Chondrosarcoma Metastasis Research Articles

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Hypoxia-regulated exosomes mediate M2 macrophage polarization and promote metastasis in chondrosarcoma.

Chondrosarcoma is a primary malignant bone tumor. Traditional therapy is not very effective, and it is prone to metastasis in the late stage. The tumor microenvironment (TME) plays a key role in the progression and metastasis of chondrosarcoma, and hypoxia is one of the key factors in the formation of TME. However, the detailed mechanism of how hypoxia affects tumor progression and metastasis in chondrosarcoma is still not fully understood. In this study, we focused on the mechanism of interaction between hypoxic chondrosarcoma cells (SW1353) and macrophages. Our results suggest that hypoxia enhances the release of exosomes from chondrosarcoma cells. These hypoxia-induced exosomes promoted macrophage polarization towards the M2 phenotype, characterized by the expression of CD163 and CD206, but not the M1 phenotype, characterized by CD86 expression. Further analysis revealed that M2 macrophages polarized by exosomes expressed arginase-1 and feedback to chondrosarcoma cells to promote migration. These results suggest that chondrosarcoma cells secrete more exosomes in a hypoxic microenvironment, and these hypoxia-derived exosomes induce the polarization of macrophages into an M2 phenotype, ultimately promoting the metastatic behavior of chondrosarcoma cells.

Risk factors for distant metastasis of Chondrosarcoma in the middle-aged and elderly people.

Chondrosarcoma is the second most common primary bone malignancy with the highest incidence in middle-aged and elderly people, where distant metastasis (DM) still leads to poor prognosis. The purpose of this study was to construct a nomogram for studying the diagnosis of DM in middle-aged and elderly patients with chondrosarcoma. Data on chondrosarcoma patients aged ≥ 40 years diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The data were divided into a training set and an internal validation set according to a 7:3 ratio, and the training set data were screened for independent risk factors for DM in chondrosarcoma patients using univariate and multivariate logistic regression analysis. The screened independent risk factors were then used to build a nomogram. In addition, data from 144 patients with chondrosarcoma aged ≥ 40 years diagnosed in a tertiary hospital in China from 2012 to 2021 were collected as the external validation set. The results were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis in the training set, internal validation set, and external validation set. A total of 1462 middle-aged and elderly patients with chondrosarcoma were included, and 92 (6.29%) had DM at the time of diagnosis. Independent risk factors for DM in middle-aged and elderly patients with chondrosarcoma included being married (OR: 2.119, 95% CI: 1.094-4.105), histological type of dedifferentiated chondrosarcoma (OR: 1.290, 95% CI: 1.110-1.499), high-grade tumor (OR: 1.511, 95% CI: 1.079-2.115), T3 stage (OR: 4.184, 95% CI: 1.977- 8.858), and N1 staging (OR: 5.666, 95% CI: 1.964-16.342). The area under the receiver operating characteristic curve (AUC) was 0.857, 0.820, and 0.859 in the training set, internal validation set, and external validation set, respectively. The results of the calibration curve and decision curve analysis also confirmed that the established nomogram could accurately predict DM in middle-aged and elderly patients with chondrosarcoma. Married, histological type of dedifferentiated chondrosarcoma, high-grade tumor, T3 stage, and N1 stage are independent risk factors for DM in middle-aged and elderly chondrosarcoma patients, and clinicians should see more attention.

Risk factors for distant metastasis of chondrosarcoma: A population-based study.

Chondrosarcoma is the second largest bone malignancy after osteosarcoma and mainly affects middle-aged adults, where patients with distant metastasis (DM) often have a poor prognosis. Although nomograms have been widely used to predict distant tumor metastases, there is a lack of large-scale data studies for the diagnostic evaluation of DM in chondrosarcoma. Data on patients diagnosed with chondrosarcoma from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Independent risk factors for having DM from chondrosarcoma were screened using univariate and multivariate logistics regression analysis. A nomogram was created to predict the probability of DM from the screened independent risk factors. The nomogram was then validated using receiver operating characteristic curves and calibration curves. A total of 1870 chondrosarcoma patients were included in the study after data screening, of which 157 patients (8.40%) had DM at the time of diagnosis. Univariate and multivariate logistic regression analysis screened four independent risk factors, including grade, tumor number, T stage, and N stage. receiver operating characteristic curves and calibration curves showed good accuracy of the nomogram in both training and validation sets. The current study screened for independent risk factors for DM from chondrosarcoma, which will help clinicians evaluate patients.

Melatonin inhibits chondrosarcoma cell proliferation and metastasis by enhancing miR-520f-3p production and suppressing MMP7 expression.

Chondrosarcoma has a high propensity to metastasize and responds poorly to chemotherapy and radiation treatment. The enzymatic activity of matrix metalloproteinases (MMPs) is very important in chondrosarcoma metastasis. Melatonin exhibits anticarcinogenic activity in many types of cancers by suppressing the expression of certain MMP family members, but this has not yet been clearly determined in chondrosarcoma. Our study demonstrates that MMP7 plays an essential role in chondrosarcoma cell proliferation, migration, and anoikis resistance. We also found that MMP7 is highly expressed in chondrosarcomas. Our in vitro and in vivo investigations show that melatonin strongly inhibits chondrosarcoma cell proliferation, migration, and anoikis resistance by directly suppressing MMP7 expression. Melatonin reduced MMP7 synthesis by promoting levels of miR-520f-3p expression, which were downregulated in human chondrosarcoma tissue samples. Pharmacological inhibition of miR-520f-3p markedly reversed the effects of melatonin upon chondrosarcoma proliferation and metastasis. Thus, our study suggests that melatonin has therapeutic potential for reducing the tumorigenesis and metastatic potential of chondrosarcoma via the miR-520f-3p/MMP7 axis.

Metástase de condrossarcoma simulando tumor primário de estômago: relato de caso

Gastric tumors are an important cause of cancer deaths. The main type is the primary gastric adenocarcinoma, and rarely secondary metastatic implants can be present. A 79-years-old woman sought medical attention due to a complaint of epigastralgia, unintentional weight loss, two cases of melena in the past two months, and a prior history of a chondrosarcoma of the thigh treated 13 years before. A neoplastic lesion was detected at the stomach during evaluation, and a gastrectomy was opted as a treatment. The immunohistochemical evaluation was compatible with a chondrosarcoma metastatic implant on the stomach. The patient obtained a survival superior to 5 years after surgery. Only one case of gastric metastasis from chondrosarcoma was described in the literature. We observed a great benefit in the use of surgical resection of the gastric lesion, showing that surgery may be considered in selected individuals with chondrosarcoma metastasis.

Mice with Trp53 and Rb1 deficiency in chondrocytes spontaneously develop chondrosarcoma via overactivation of YAP signaling

Chondrosarcoma (CHS) is a rare type of soft sarcoma with increased production of cartilage matrix arising from soft bone tissues. Currently, surgical resection is the primary clinical treatment for chondrosarcoma due to the poor response to radiotherapy and chemotherapy. However, the therapeutic effect is not satisfactory due to the higher local recurrence rate. Thus, management and elucidation of the pathological mechanism of chondrosarcoma remain an ongoing challenge, and the development of effective chondrosarcoma mouse models and treatment options are urgently needed. Here, we generated a new transgenic chondrosarcoma model by double conditional deletions of Trp53 and Rb1 in chondrocyte lineage which spontaneously caused spinal chondrosarcoma and lung metastasis. Bioinformatic analysis of the human soft sarcoma database showed that Trp53 and Rb1 genes had higher mutations, reaching up to approximately 33.5% and 8.7%, respectively. Additionally, Trp53 and Rb1 signatures were decreased in the human and mouse chondrosarcoma tissues. Mechanistically, we found that YAP expression and activity were significantly increased in mouse Col2-Cre;Trp53f/f/Rb1f/f chondrosarcoma tissues compared to the adjacent normal cartilage. Knockdown of YAP in primary chondrosarcoma cells significantly inhibited chondrosarcoma proliferation, invasion, and tumorsphere formation. Chondrocyte lineage ablation of YAP delayed chondrosarcoma progression and lung metastasis in Col2-Cre;Trp53f/f/Rb1f/f mice. Moreover, we found that metformin served as a YAP inhibitor, which bound to the activity area of YAP protein, and inhibited chondrosarcoma cell proliferation, migration, invasion, and progression in vitro and significantly suppressed chondrosarcoma formation in vivo. Collectively, this study identifies the inhibition of YAP may be an effective therapeutic strategy for the treatment of chondrosarcoma.

Uniportal VATS Pleural Biopsy: Analysis of 50 Cases Is It Safe and Effective ?

Objective: Pleural effusion may occur in patients due to benign or malignant processes. This study aimed to evaluate the efficacy and safety of Uniportal Video-Assisted Thoracoscopic Surgery (VATS) operation in the diagnosis processes of patients with pleural effusion.Methods: The data of 50 patients who underwent diagnostic Uniportal VATS pleural biopsy between November 2018 and April 2021 were retrospectively analyzed. The patients' age, gender, postoperative hospital stay, operation-related complications, and pathology results of the pleural tissues were recorded.Results: Thirty-five (70%) cases were male, 15 (30%) were female, mean age was 52.58 ± 20.1, mean operative time was 56.1 ± 16.8 minutes, and mean postoperative hospital stay was 2.64 ± 0.89 days. 48 (96%) of the patients were operated on under general anesthesia and 2 (4%) under sedative anesthesia. All patients were operated on with the Uniportal VATS technique. The postoperative treatment process was carried out with service follow-up without requiring intensive care follow-up. Twenty-eight (56%) patients were operated on from the right and 22 (44%) patients from the left hemithorax. When the pleural biopsy results were examined, malignancy was detected in 18 (36%) patients and tuberculosis in 8 (16%). Malignancies: 6 were adenocancer metastases (2 stomachs, 2 breast, and 2 colon cancers), 5 malignant mesotheliomas, 4 epidermoid cancer metastases (2 ovarian and 1 breast and 1 malignant melanoma), 2 lung adenocarcinoma infiltration, and 1 chondrosarcoma metastasis. No postoperative complications were observed in any of the patients.Conclusion: Uniportal VATS is an easy-to-apply, safe, effective, and rapid method for diagnosing pleural effusion.

Risk Analysis of Distal Metastasis in Chondrosarcoma and the Development and Validation of a Novel Clinical Prediction Model: A Clinical Study Based on the SEER Database

Purpose. Distal metastasis in chondrosarcoma is associated with a poor prognosis. The aim of this study was to develop and validate columnar maps to predict the risk of distal metastasis in patients with chondrosarcoma, thereby contributing to clinical diagnosis and treatment. Methods. Data from chondrosarcoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016 were then screened by univariate and multifactorial logistic regressions to construct a predictive distal metastasis risk. The model discrimination of nomogram was assessed by calibration plots, while the predictive accuracy and clinical values were measured by decision curve analysis (DCA). In addition, predictive column line plots were validated in an in-house test set. Results. A total of 1,290 patients were included and randomized in a 7 to 3 ratio into a training group (n = 906) and a test group (n = 384). After logistic regression analysis, the significant variables were gender, tumor pathological grade, laterality, primary tumor stage, regional lymph node metastasis, surgical treatment, and chemotherapy. Calibration curves showed agreement between column line graph predictions and actual observations, while DCA showed the clinical utility of the nomogram. In addition, ROC showed good discrimination and calibration in the training (AUC = 0.937, 95% CI 0.919–0.952) and validation groups (AUC = 0.91, 95% CI 0.877–0.937). Conclusions. The nomogram for distal metastasis risk in patients with chondrosarcoma can effectively predict the individualized risk of distal metastasis and provide clinicians with enlightening information to optimize treatment options.

WISP-3 Stimulates VEGF-C-Dependent Lymphangiogenesis in Human Chondrosarcoma Cells by Inhibiting miR-196a-3p Synthesis.

Chondrosarcoma is a malignant bone tumor with high metastatic potential. Lymphangiogenesis is a critical biological step in cancer metastasis. WNT1-inducible signaling pathway protein 3 (WISP-3) regulates angiogenesis and facilitates chondrosarcoma metastasis, but the role of WISP-3 in chondrosarcoma lymphangiogenesis is unclear. In this study, incubation of chondrosarcoma cells with WISP-3 increased the production of VEGF-C, an important lymphangiogenic factor. Conditioned medium from WISP-3-treated chondrosarcoma cells significantly enhanced lymphatic endothelial cell tube formation. WISP-3-induced stimulation of VEGF-C-dependent lymphangiogenesis inhibited miR-196a-3p synthesis in the ERK, JNK, and p38 signaling pathways. This evidence suggests that the WISP-3/VEGF-C axis is worth targeting in the treatment of lymphangiogenesis in human chondrosarcoma.

Visfatin Promotes the Metastatic Potential of Chondrosarcoma Cells by Stimulating AP-1-Dependent MMP-2 Production in the MAPK Pathway.

Chondrosarcoma is a malignant bone tumor that is characterized by high metastatic potential and marked resistance to radiation and chemotherapy. The knowledge that adipokines facilitate the initiation, progression, metastasis, and treatment resistance of various tumors has driven several in vitro and in vivo investigations into the effects of adipokines resistin, leptin, and adiponectin upon the development and progression of chondrosarcomas. Another adipokine, visfatin, is known to regulate tumor progression and metastasis, although how this molecule may affect chondrosarcoma metastasis is unclear. Here, we found that visfatin facilitated cellular migration via matrix metalloproteinase-2 (MMP-2) production in human chondrosarcoma cells and overexpression of visfatin enhanced lung metastasis in a mouse model of chondrosarcoma. Visfatin-induced stimulation of MMP-2 synthesis and activation of the AP-1 transcription factor facilitated chondrosarcoma cell migration via the ERK, p38, and JNK signaling pathways. This evidence suggests that visfatin is worth targeting in the treatment of metastatic chondrosarcoma.

Immunohistochemically detectable thyroglobulin expression in extrathyroidal cancer is 100% specific for thyroidal tumor origin

Thyroglobulin is a secreted 660 kDa glycoprotein produced by thyroid follicular cells used in diagnostic pathology to secure or exclude a thyroidal origin of metastases of unknown primary tumors. This study was performed to estimate specificity of thyroglobulin immunohistochemistry. 9974 tumor samples from 109 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. Thyroglobulin was strongly expressed in all normal thyroid samples but not in any other normal tissues. Thyroglobulin immunostaining was detected in 99.1% of 106 thyroid adenomas, 98.1% of 364 papillary, 95.2% of 147 follicular, and 7.5% of 40 anaplastic thyroid cancers. Twelve of 15 thyroid samples that were thyroglobulin negative on TMAs showed at least a weak focal thyroglobulin positivity in corresponding large sections, suggesting higher sensitivity of large section analysis. Thyroglobulin positivity in one diffuse large B-cell lymphoma of the thyroid, one chondrosarcoma metastasis to the thyroid, and 42.4% of 92 medullary thyroid cancers was considered to be caused by diffusion of thyroidal colloid from destroyed or even intact adjacent follicles. Thyroglobulin positivity was, however, not seen in 6403 extrathyroidal tumors from 104 different tumor types and subtypes. Our data demonstrate a complete specificity of positive thyroglobulin immunostaining for thyroid origin in tumor tissues obtained from extrathyroidal locations. However, for all tumors located within the thyroid, false positivity can occur as a result of tissue contamination by thyroglobulin rich thyroid colloid from adjacent normal tissue.

The mir-423-5p/MMP-2 Axis Regulates the Nerve Growth Factor-Induced Promotion of Chondrosarcoma Metastasis

Simple SummaryA chondrosarcoma is a common tumor of the bone that has a high propensity to metastasize to distant organs. The effects of NGF in a chondrosarcoma are not confirmed although NGF is capable of promoting the progression and metastasis of several different types of tumors. Here, we found that NGF promotes the chondrosarcoma migration and metastasis in vitro and in vivo. The levels of NGF and MMP-2 in human chondrosarcoma tumor tissues correlated strongly with the tumor stage. We identified that NGF induces the MMP-2 synthesis and chondrosarcoma cell motility by inhibiting miR-423-5p expression through the FAK and c-Src pathways. We suggest that NGF is a worthwhile therapeutic target in the treatment of a metastatic chondrosarcoma.A chondrosarcoma is a common tumor of the soft tissue and bone that has a high propensity to metastasize to distant organs. Nerve growth factor (NGF) is capable of promoting the progression and metastasis of several different types of tumors although the effects of NGF in a chondrosarcoma are not confirmed. Here, we found that the levels of NGF and matrix metalloproteinase-2 (MMP-2) correlated with the tumor stage in patients with a chondrosarcoma. NGF facilitated the MMP-2-dependent cellular migration in human chondrosarcoma JJ012 cells while the overexpression of NGF enhanced the lung metastasis in a mouse model of a chondrosarcoma. NGF promoted the MMP-2 synthesis and cell migration by inhibiting miR-423-5p expression through the FAK and c-Src signaling cascades. NGF appears to be a worthwhile therapeutic target in the treatment of a metastatic chondrosarcoma.

Risk analysis of pulmonary metastasis of chondrosarcoma by establishing and validating a new clinical prediction model: a clinical study based on SEER database

BackgroundThe prognosis of lung metastasis (LM) in patients with chondrosarcoma was poor. The aim of this study was to construct a prognostic nomogram to predict the risk of LM, which was imperative and helpful for clinical diagnosis and treatment.MethodsData of all chondrosarcoma patients diagnosed between 2010 and 2016 was queried from the Surveillance, Epidemiology, and End Results (SEER) database. In this retrospective study, a total of 944 patients were enrolled and randomly splitting into training sets (n = 644) and validation cohorts(n = 280) at a ratio of 7:3. Univariate and multivariable logistic regression analyses were performed to identify the prognostic nomogram. The predictive ability of the nomogram model was assessed by calibration plots and receiver operating characteristics (ROCs) curve, while decision curve analysis (DCA) and clinical impact curve (CIC) were applied to measure predictive accuracy and clinical practice. Moreover, the nomogram was validated by the internal cohort.ResultsFive independent risk factors including age, sex, marital, tumor size, and lymph node involvement were identified by univariate and multivariable logistic regression. Calibration plots indicated great discrimination power of nomogram, while DCA and CIC presented that the nomogram had great clinical utility. In addition, receiver operating characteristics (ROCs) curve provided a predictive ability in the training sets (AUC = 0.789, 95% confidence interval [CI] 0.789–0.808) and the validation cohorts (AUC = 0.796, 95% confidence interval [CI] 0.744–0.841).ConclusionIn our study, the nomogram accurately predicted risk factors of LM in patients with chondrosarcoma, which may guide surgeons and oncologists to optimize individual treatment and make a better clinical decisions.Trial registrationJOSR-D-20-02045, 29 Dec 2020.

Hemivertebrectomy of L5 in Grade 2 Chondrosarcoma: Is a Single Posterior Approach with No Nerve Root Sacrifice Possible? A Case Report

En-bloc resection of spine tumors is difficult to achieve compared to extremities tumors for anatomical reason. Several surgical techniques have been described, such as combined multiple surgical approaches or an enlarged single posterior approach. These demanding strategies correlate with high rate of intraoperative/postoperative complications. The current case is about a patient treated with a single posterior-lateral surgical approach to perform hemivertebrectomy of L5 for a single grade 2 chondrosarcoma metastasis (WBB 2-5/b-c). Usually, L5 hemivertebrectomy requires a combined surgical approach to preserve L5 root. The final solution was to perform a T-shape skin incision: a longitudinal branch centered on the vertebral spine and a transverse branch on the iliac crest. This approach allowed osteotomy of the ipsilateral iliac crest, achieving sufficient view to preserve L5 root and vessels anteriorly; the same osteotomy was used to create a bone autograft to reconstruct the residual part of L5. Finally, cryotherapy was used in order to increase the adequacy of surgical margins. A L3-S1 arthrodesis is assembled to achieve stability of the system. Surgical time was 5 hours, no nerve roots have been sacrificed nor any other intraoperative complications occurred. This surgical technique had never been described before in literature.

Inhibitory effects on chondrosarcoma cell metastasis by Senna alata extract

BackgroundSenna alata L. Roxb or candle bush is a traditional medicinal plant with a wide range of biological activities including anti-inflammatory, antimicrobial and antifungal. Leaf extract of S. alata showed the anti-tumor activity in various cancer cell lines. In this study, we focused on the inhibitory mechanism of S. alata extract (SAE) on cancer metastasis including cell migration, cell invasion and signaling pathways in chondrosarcoma SW1353 cells. PurposeThis study aimed to evaluate the anti-metastatic mechanisms of Senna alata extract on chondrosarcoma SW1353 cells. MethodsScreening for phytochemicals in biologically active fraction of SAE was analysed by 1H NMR spectroscopy. Cell viability and cytoxicity were determined by using MTT assay. Cell migration was observed by scratch wound healing and transwell migration assay. Cell invasion and cell adhesion assay were examined by Matrigel coated transwell chambers or plates. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), MAPKs and PI3K/Akt signaling pathways and NF-κB were detected by Western blot analysis. ResultsThe SAE treatment at the sub-cytoxic and non-cytotoxic concentrations significantly inhibited cell migration, cell invasion and cell adhesion of SW1353 cells in a dose-dependent manner. The results from Western blot analysis showed decreased MMP-2 and MMP-9 expression, while increased TIMP-1 and TIMP-2 expression in SAE treated cells. Moreover, SAE suppressed phosphorylation of ERK1/2, p38 and Akt but decreased NF-κB transcription factor expression in SW1353 cells. ConclusionThese results revealed that SAE could reduce MMP-2 and MMP-9 expression by downregulation of NF-κB which is downstream of MAPKs and PI3K/Akt signaling pathway in SW1353 cells resulting in reduced cancer cell migration and invasion. Therefore, SAE may have the potential use as an alternative treatment of chondrosarcoma metastasis.

Chondrosarcoma local recurrence in the Cancer Registry of Norway cohort (1990-2013): Patterns and impact.

There appears to be an association between local recurrence (LR) and risk of metastasis and death in central conventional chondrosarcoma (CCCS) of bone, but this has not been quantified in modern cohorts at a subtype level. We identified nonmetastatic cases of CCCS (N = 180) from the Cancer Registry of Norway. We present prognostic analysis of LR accounting for immortal time bias by descriptive statistics and multivariable Cox models. Of 40 LR, one case demonstrated upgrading while two dedifferentiation. LR was associated with increased risk of metastasis (hazard ratio [HR] = 4.1 [confidence interval, 1.5-10.7]) and death (HR = 9.3 [5.0-17.5]) overall. LR was associated with significant increased risk of metastasis for those with a soft tissue component, axial location, malignancy grade 2, but not atypical cartilaginous tumor's, appropriately treated curettage patients, intramedullary tumors, grade 1 histology, extremity location or "Oslo low risk" group status. We found an increased risk of death for all groups except for those treated by appropriate curettage or belonging to the "Oslo low risk" group. About 50% of LR CCCS were asymptomatic and revealed by routine follow-up. Upgrading of LR for CCCS was a seldom event. LR was associated with significant increased risk of metastasis and death overall, but not for appropriately treated curettage patients or "Oslo low risk" status.

Pancreatic metastasis of mesenchymal chondrosarcoma

Mesenchymal chondrosarcoma is an aggressive tumor with chondrogenic differentiation that typically develops in skeletal sites, such as craniofacial bones, ribs, ilium, femur, and the vertebrae. It counts less than 3% of primary chondrosarcomas, and about a third of these tumors develop extraskeletal sites such as the meninges, and soft tissue. We present a case of a 53-year-old female, that was diagnosed with mesenchymal chondrosarcoma in the left thigh and submitted to surgical excision. The patient's case was evaluated by a multidisciplinary team, and it was decided to maintain vigilance. In the 5 years, follow-up presented several pulmonary metastases that were submitted to pulmonary resections. Two years later, during imaging control, an abdominal computed tomography (CT) scan was performed and revealed a pancreatic mass of 3 centimeters, located in the pancreatic tail. The patient was submitted to an explorative laparoscopy and a distal pancreatectomy was performed. The biopsy gave the definitive result of the metastasis of mesenchymal chondrosarcoma.

Abstract 4915: Nerve growth factor (NGF) facilitates LOX expression and promotes tumor metastasis by inhibiting miR-149-5p in human chondrosarcoma cells

Abstract Chondrosarcomas are malignant bone tumors that commonly produce cartilaginous chondroid matrix and are associated with metastases in the lung, especially in patients with high-grade chondrosarcoma. Neurotrophins such as nerve growth factor (NGF) are recognized as being drivers of neurogenesis during development and regeneration, and their expression in human tumors can stimulate cancer cell growth. Importantly, the infiltration of nerves in the tumor microenvironment actively stimulates cancer cell mitogenesis, invasiveness and metastasis. Until now, it has been unclear as to the potential involvement of NGF in human chondrosarcoma metastasis. This study reports that NGF induces migration and invasion of chondrosarcoma cell lines JJ012 and SW1353 and significantly increasing LOX expression. Significant dose-dependent increases were observed in levels of LOX mRNA and protein expression in both cell lines. In immunohistochemistry analyses, levels of NGF and LOX expression in human chondrosarcoma cartilage correlated with tumor stage and were substantially higher than NGF and LOX expression in normal cartilage. NGF-induced stimulation of metastasis and increases in LOX expression were prevented by pretreatment of the cell lines with PI3K, Akt and mTOR inhibitors, or transfection with small interfering RNAs (siRNAs). Further analysis revealed that NGF induced PI3K/Akt/mTOR signaling and dose-dependently downregulated mature microRNA-149-5p (miR-149-5p), which targets the 3' untranslated region (3'-UTR) of LOX. Furthermore, JJ012 cells overexpressing NGF induced LOX expression and increased cell migration and invasion. In summary, NGF stimulates LOX expression and promotes chondrosarcoma cell migration and invasion by inhibiting miR-149-5p via the PI3K/Akt/mTOR signaling pathway. Citation Format: Anoop Thadevoos Louis, Chih-Yang Lin, Chih-Hsin Tang. Nerve growth factor (NGF) facilitates LOX expression and promotes tumor metastasis by inhibiting miR-149-5p in human chondrosarcoma cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4915.

Lymph node metastasis in extremity chondrosarcomas: A series of four cases.

Background:Primary bone sarcomas mainly metastasize through haematogenous route and rarely through lymph nodes due to paucity of lymphatic channels in the bone (1). Nodal spread in chondrosarcoma is extremely rare and there are two reported cases in literature including one previously published by our institute (3, 5).Aims and Objectives:We present a series of chondrosarcoma cases (primary tumour located in the scapula, proximal femur, proximal humerus and pelvis), presenting with lymph node metastasis, treated at our institute. We assessed the oncological outcome of these cases and the impact of nodal metastasis on survival.Materials and Methods:Between January 2006 and December 2015, 243 patients of extremity and pelvic chondrosarcoma were operated at our institute. These cases were retrieved from a prospectively maintained database. Four (1.6%) of these patients developed lymph node metastasis. Clinical and radiological details of these cases were retrieved from electronic medical records and case files. Histopathology of the primary chondrosarcoma lesion and nodal metastasis was reconfirmed by a pathologist specializing in sarcomas.Conclusion:Lymph node metastasis though extremely rare in primary osseous chondrosarcoma, definitely affects their survival adversely. The rarity of the occurrence of lymph node metastasis in primary osseous tumors, especially chondrosarcoma highlights the need for multi institutional studies to pool knowledge and evaluate the prognostic significance and etiopathogenesis of lymph node metastasis in primary bone chondrosarcoma.