Tumor Cell Mass Research Articles

Lentinan-based pH-responsive nanoparticles achieve the combination therapy of tumors

Cancer poses a significant threat to human health, and there is an urgent need for more effective treatments. Combining chemotherapy and immunotherapy is an effective strategy to enhance curative outcomes and holds great potential for widespread application. The natural phytochemical genistein (GEN) exhibits cytotoxicity against tumors and is a potential chemotherapeutic agent. Lentinan (LTN) is a natural polysaccharide with immune-enhancing properties that has been utilized in tumor treatment. This study constructed a pH-responsive nanoparticle GEN@LTN-BDBA with chemotherapy and immunotherapy functions using GEN and LTN. After characterizing the nanoparticles, the molecular mechanism of GEN@LTN-BDBA formation was explored using in silico simulation. GEN@LTN-BDBA can significantly inhibit the proliferation of A549 and HepG2 cells in vitro. The in vivo experiment results demonstrated that treatment with GEN@LTN-BDBA can significantly reduce tumor cell mass and prevent metastasis. In this nanoparticle, GEN induced oxidative stress and apoptosis of tumor cells. Meanwhile, the released LTN initiated an anti-tumor immune response by promoting dendritic cell (DC) maturation and upregulating the expression of costimulatory molecules and major histocompatibility complex. The construction method of GEN@LTN-BDBA can be extended to the preparation of other polysaccharides and hydrophobic chemotherapy molecules, offering a novel strategy to enhance the efficacy of monotherapy.

A rare case of concomitant endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis

BackgroundCarcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium.Case presentationThis case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy.ConclusionWe herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.

Tumor Dormancy and Reactivation: The Role of Heat Shock Proteins.

Tumors are a heterogeneous group of cell masses originating in various organs or tissues. The cellular composition of the tumor cell mass interacts in an intricate manner, influenced by humoral, genetic, molecular, and tumor microenvironment cues that dictate tumor growth or suppression. As a result, tumors undergo a period of a dormant state before their clinically discernible stage, which surpasses the clinical dormancy threshold. Moreover, as a genetically imprinted strategy, early-seeder cells, a distinct population of tumor cells, break off to dock nearby or extravasate into blood vessels to secondary tissues, where they form disseminated solitary dormant tumor cells with reversible capacity. Among the various mechanisms underlying the dormant tumor mass and dormant tumor cell formation, heat shock proteins (HSPs) might play one of the most important roles in how the dormancy program plays out. It is known that numerous aberrant cellular processes, such as malignant transformation, cancer cell stemness, tumor invasion, metastasis, angiogenesis, and signaling pathway maintenance, are influenced by the HSPs. An accumulating body of knowledge suggests that HSPs may be involved in the angiogenic switch, immune editing, and extracellular matrix (ECM) remodeling cascades, crucial genetically imprinted strategies important to the tumor dormancy initiation and dormancy maintenance program. In this review, we highlight the biological events that orchestrate the dormancy state and the body of work that has been conducted on the dynamics of HSPs in a tumor mass, as well as tumor cell dormancy and reactivation. Additionally, we propose a conceptual framework that could possibly underlie dormant tumor reactivation in metastatic relapse.

Case of Pulmonary Tumor Embolism due to Oropharyngeal Carcinoma Diagnosed by a Transbronchial Lung Biopsy.

Pulmonary tumor embolisms (PTEs) are primarily caused by adenocarcinoma. However, only a few cases of oropharyngeal carcinoma have been reported. We herein report a 47-year-old man who presented with a fever, cough, and dyspnea 6 months after treatment for stage II oropharyngeal carcinoma. Chest computed tomography revealed centrilobular granular and nodular shadows and subpleural consolidation. A transbronchial lung biopsy revealed a mass of squamous tumor cells forming emboli in the small vessels, resulting in the diagnosis of PTE due to oropharyngeal carcinoma. Therefore, PTE should be considered for patients with a history of hypoxia.

The effectiveness of moderate intensity continuous exercises and nano-curcumin supplementation on sensory-motor disorders in Rats with brain tumors

Background and Objectives:Any abnormal growth of cells in the brain in an uncontrolled manner leads to the formation of tumor cell masses and disruption of the normal functional functions of the brain, including sensory-motor problems. The aim of the present study was to evaluate the The effectiveness of moderate-intensity continuous exercise and nanocurcumin supplementation on sensorimotor disorders in mice with brain tumors. Subjects and Methods: 35 healthy male Wistar rats randomly divided into 7 groups of 5, basal control (BC), 4-week control (4wC), basal cancer control(BT), 4-week cancer control(4wT), cancer-training (TE), cancer - Nanocurcumin (TN), Cancer-Exercise-Nanocurcumin (TEN) were divided. One week after the injection of cancer cells in the frontal cortex, the animals entered the main exercise program on the tape by performing the 6-parameter behavioral test (18 points) of Garcia and gavage of nano curcumin supplement at the rate of 80 mg/kg (28 days, 5 days a week). (4 weeks, at a speed of 18 meters per minute, 25-40 minutes and 3 days a week). At the end, rats were victim and data were collected and analyzed. Result: Continuous exercises with moderate intensity Simultaneously with nano-curcumin supplementation significantly reduced tumor volume in the TEN group (p≤0.05). It also led to a significant increase in behavioral testing in the study groups compared to the 4 wT group. Conclusion: It seems that the combination of continuous exercises with nano curcumin can be used as a therapeutic supplement along with other methods to reduce brain tumor size and improve sensory-motor functions.

Tumor Microenvironment as a Therapeutic Target in Melanoma Treatment.

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma.

Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.

Nasopharyngeal carcinoma (NPC), the most frequent reason for treatment failure in head and neck tumors, has the greatest incidence of distant metastases. Increased vascular permeability facilitates metastasis. Exosomal microRNAs (miRNAs) have been implicated in the development of the premetastatic niche and are emerging as prospective biomarkers in cancer patients. We discovered that a higher level of miR-455 was connected to a larger propensity for NPC metastasis based on deep sequencing and RT-qPCR. We found that hypoxia promoted NPC exosomes release and increased miR-455 expression in a way that was hypoxia-inducible factor 1-alpha(HIF-1α) dependent. Exosomes from NPC cells with high levels of miR-455 were found to specifically target zonula occludens 1 (ZO-1), increasing the permeability of endothelial monolayers in vitro vascular permeability and transendothelial invasion experiments. Additional in vivo studies showed that zebrafish with sustained miR-455-overexpressing NPC cell xenografts displayed increased tumor cell mass throughout the body. In vivo, zebrafish vascular tight junctionintegrity was disrupted by exosomes produced by NPC cells with elevated miR-455 expression. Mice-bearing xenografts further supported the finding that exosomes containing miR-455 might reduce ZO-1 expression in addition to promote NPC cell growth. These findings suggest that in a hypoxic microenvironment, exosomal miR-455 released by NPC cells enhances vascular permeability and promotes metastasis by targeting ZO-1. The HIF-1α-miR-455-ZO-1 signaling pathway may be a promising predictor and potential therapeutic target for NPC with metastasis.

Oncolytic adenovirus-mediated expression of CCL5 and IL12 facilitates CA9-targeting CAR-T therapy against renal cell carcinoma

Chimeric antigen receptor T-cell (CAR-T) is particularly prominent in hematological but not in solid tumors, mainly based on the complex tumor immune microenvironment. Oncolytic virus (OVs) is an emerging adjuvant therapy method. OVs may prime tumor lesions to induce anti-tumor immune response, thereby enhancing CAR-T cells functionality and possibly increasing response rates. Here, we combined CAR-T cells targeting carbonic anhydrase 9 (CA9) and an oncolytic adenovirus (OAV) carrying chemokine (C-C motif) ligand 5 (CCL5), cytokine interleukin-12 (IL12) to explore the anti-tumor effects of this combination strategy. The data showed that Ad5-ZD55-hCCL5-hIL12 could infect and replicate in renal cancer cell lines and induced a moderate inhibition of xenografted tumor in nude mice. IL12 mediated by Ad5-ZD55-hCCL5-hIL12 promoted the phosphorylation of Stat4 in CAR-T cells, induced CAR-T cells to secrete more IFN-γ. We also found that Ad5-ZD55-hCCL5-hIL-12 combined with CA9-CAR-T cells significantly increased the infiltration of CAR-T cells in tumor mass, prolonged the survival of the mice and restrained tumor growth in immunodeficient mice. Ad5-ZD55-mCCL5-mIL-12 could also increase CD45+CD3+T cell infiltration and prolong mice survival in immunocompetent mice. These results provided feasibility for the combination of oncolytic adenovirus and CAR-T cells, which demonstrated the sufficient potential and prospects of CAR-T for the treatment of solid tumors.

A Comparative Study of Seven Machine Learning Algorithms for Breast Cancer Detection and Diagnosis

This paper presents a comparative analysis of seven distinct machine learning (ML) algorithms, namely Linear Discriminant Analysis, Logistic Regression, K-Nearest Neighbor, Decision Tree Classifier, Random Forest Classifier, Voting Classifier, and Support Vector Machine, in predicting the diagnosis of breast cancer. The study utilized 30 histological tumor features obtained from digital imaging of fine needle aspirates of breast tumor cell masses contained in the dataset, achieving an accuracy of approximately 95% through the application of the aforementioned algorithms. Results show that the LDA and RFC algorithms outperformed the others in terms of accuracy in diagnosing breast cancer. Furthermore, the study suggests that the stability of diagnostic outcomes is better achieved with large-scale data. Finally, the accuracy of the LR algorithm was observed to be less than 85% after conducting Principal Component Analysis (PCA), which was lower than the accuracy achieved without dimensionality reduction.

P043: Molecular pathogenesis of Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is one of the most frequent lymphomas in the Western world. Its malignant Hodgkin and Reed/Sternberg (HRS) cells are derived from pre-apoptotic germinal center B cells and only account for ca. 1% of the tumor cell mass. The surrounding inflammatory infiltrate is unable to establish an effective immune response against the HRS cells. To better understand HRS cell formation and their molecular pathogenesis, we aim to determine the mutational landscape of HRS cells. HRS cells of a total of 30 cases were isolated by microdissection or flow cytometry and subjected to exome or whole-genome sequencing. We confirmed recurrently mutated genes (e.g. SOCS1, TNFAIP3) but also found novel promising genes such as NLRC5, which is involved in MHCI expression and negative NFkB regulation. Intriguingly, mutational signatures associated with APOBEC and somatic hypermutation were identified. Moreover we are currently analyzing the WGS samples for mutations in gene regulatory regions, miRNA binding sites and gains and losses. Both WGS and WES show a wide variation in their mutational loads.

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours.

Simple SummaryUsing immune cells to treat cancers is a promising new approach for leukemias and lymphomas. However, the use of cellular therapy in solid tumours is compromised by poor migration to the tumour, the physical barriers to infiltration, and the active suppression by the tumour. We will review both past and emerging strategies that could be used to enhance the migration and infiltration of adoptively transferred cell types, including CAR NK and T cells, in solid tumour immunotherapy.The precision guiding of endogenous or adoptively transferred lymphocytes to the solid tumour mass is obligatory for optimal anti-tumour effects and will improve patient safety. The recognition and elimination of the tumour is best achieved when anti-tumour lymphocytes are proximal to the malignant cells. For example, the regional secretion of soluble factors, cytotoxic granules, and cell-surface molecule interactions are required for the death of tumour cells and the suppression of neovasculature formation, tumour-associated suppressor, or stromal cells. The resistance of individual tumour cell clones to cellular therapy and the hostile environment of the solid tumours is a major challenge to adoptive cell therapy. We review the strategies that could be useful to overcoming insufficient immune cell migration to the tumour cell mass. We argue that existing ‘competitive’ approaches should now be revisited as complementary approaches to improve CAR T and NK cell therapy.

An Unusual Case

Intravenous leiomyomatosis (IVL) is a rare neoplasm characterized by histologically benign-looking smooth muscle cell tumor mass which grows within the intrauterine and extrauterine venous system. In this report, we present an unusual case of IVL which had originated from uterus and extended throughout the right cardiac chambers. A 36-year-old female patient came with a chief complaint of palpitation for 1-month duration. She also had a history of amenorrhea for 7 months. She had abdominal distension and doughy feeling of the abdomen. Seven months prior, ultrasound abdomen done during gynecological evaluation showed fibroid uterus. Echocardiography done showed multiple masses occupying almost all of the right atrium and moving in and out of the right ventricle. Inferior vena cava (IVC) was dilated and 90% of the IVC was filled with the mass. Cardiothoracic surgery and surgical oncology references were done. The patient was planned for simultaneous abdominal and cardiothoracic surgery. Large abdominal mass along with cardiac mass was resected along with mesentery, omentum, and abdominal lymph nodes. Histopathological and microscopic report was suggestive of leiomyoma and leiomyomatosis. Lymph node microscopy showed reactive hyperplasia.

Intratumoral VEGF nanotrapper reduces gliobastoma vascularization and tumor cell mass

Glioblastoma multiforme (GBM) is the most aggressive and invasive malignant brain cancer. GBM is characterized by a dramatic metabolic imbalance leading to increased secretion of the pro-angiogenic factor VEGF and subsequent abnormal tumor vascularization. In 2009, FDA approved the intravenous administration of bevacizumab, an anti-VEGF monoclonal antibody, as a therapeutic agent for patients with GBM. However, the number of systemic side effects and reduced accessibility of bevacizumab to the central nervous system and consequently to the GBM tumor mass limited its effectiveness in improving patient survival. In this study, we combined experimental and computational modelling to quantitatively characterize the dynamics of VEGF secretion and turnover in GBM and in normal brain cells and simultaneous monitoring of vessel growth. We showed that sequestration of VEGF inside GBM cells, can be used as a novel target for improved bevacizumab-based therapy. We have engineered the VEGF nanotrapper, a cargo system that allows cellular uptake of bevacizumab and inhibits VEGF secretion required for angiogenesis activation and development. Here, we show the therapeutic efficacy of this nanocargo in reducing vascularization and tumor cell mass of GBM in vitro and in vivo cancer models.

Genomic studies of Hodgkin lymphoma using circulating cell-free DNA

The revolutionary finding of cell free DNA (cfDNA) circulating in the bloodstream had a huge impact on the development of non-invasive prenatal testing (NIPT) (obstetrics) and liquid biopsies (oncology). The latter, combined with the sequencing of tumor DNA-containing cfDNA, have been widely applied in cancer research, demonstrating the potential of these techniques to improve prognostication and guide individualized treatment strategies. During routine NIPT analysis of more than 88,000 pregnant women performed in our institution, 14 abnormal genomic profiles suggestive of maternal tumor have been identified. Interestingly, one patient was further diagnosed with classic Hodgkin lymphoma (cHL), a tumor characterized by a low content (< 2%) of neoplastic cells in tumor mass. To examine whether circulating cfDNA can be informative about genomic imbalances in neoplastic Hodgkin/Reed-Sternberg (HRS) cells, we performed a pilot study of nine prospective cHL cases. This study showed that genomic profiles of cfDNA correspond to the profiles of HRS cells. To get further insights into the genome of cHL, a large study on cfDNA from 177 prospective cHL patients was subsequently established. Based on ultra-low pass sequencing of cfDNA from this cohort, we built a comprehensive catalog of genomic abnormalities, as well as their frequencies and patterns. Besides the known recurrent imbalances, such as gain/amplification of 2p16/ REL-BCL11A and 9p24/ JAK2-CD274-PDCDLG2 , novel recurrent abnormalities were identified in cHL. Altogether, we have provided evidence that cHL is characterized by consistent and recurrent genomic imbalances and we have shown the potential of genomic profiling of cfDNA as a novel and non-invasive tool in the diagnosis and follow up of cHL patients.

Cancer Metabostemness and Metabolic Reprogramming via P2X7 Receptor.

The heterogeneity of tumor cell mass and the plasticity of cancer cell phenotypes in solid tumors allow for the insurgence of resistant and metastatic cells, responsible for cancer patients’ clinical management’s main challenges. Among several factors that are responsible for increased cancer aggression, metabolic reprogramming is recently emerging as an ultimate cancer hallmark, as it is central for cancer cell survival and self-renewal, metastasis and chemoresistance. The P2X7 receptor, whose expression is upregulated in many solid and hematological malignancies, is also emerging as a good candidate in cancer metabolic reprogramming and the regulation of stem cell proliferation and differentiation. Metabostemness refers to the metabolic reprogramming of cancer cells toward less differentiated (CSCs) cellular states, and we believe that there is a strong correlation between metabostemness and P2X7 receptor functions in oncogenic processes. Here, we summarize important aspects of P2X7 receptor functions in normal and tumor tissues as well as essential aspects of its structure, regulation, pharmacology and its clinical use. Finally, we review current knowledge implicating P2X7 receptor functions in cancer-related molecular pathways, in metabolic reprogramming and in metabostemness.

The expression of B7-H3 isoforms in newly diagnosed glioblastoma and recurrence and their functional role

Short survival of glioblastoma (GBM) patients is due to systematic tumor recurrence. Our laboratory identified a GBM cell subpopulation able to leave the tumor mass (TM) and invade the subventricular zone (SVZ-GBM cells). SVZ-GBM cells escape treatment and appear to contribute to GBM recurrence. This study aims to identify proteins specifically expressed by SVZ-GBM cells and to define their role(s) in GBM aggressiveness and recurrence. The proteome was compared between GBM cells located in the initial TM and SVZ-GBM cells using mass spectrometry. Among differentially expressed proteins, we confirmed B7-H3 by western blot (WB) and quantitative RT-PCR. B7-H3 expression was compared by immunohistochemistry and WB (including expression of its isoforms) between human GBM (N = 14) and non-cancerous brain tissue (N = 8), as well as newly diagnosed GBM and patient-matched recurrences (N = 11). Finally, the expression of B7-H3 was modulated with short hairpin RNA and/or over-expression vectors to determine its functional role in GBM using in vitro assays and a xenograft mouse model of GBM. B7-H3 was a marker for SVZ-GBM cells. It was also increased in human GBM pericytes, myeloid cells and neoplastic cells. B7-H3 inhibition in GBM cells reduced their tumorigenicity. Out of the two B7-H3 isoforms, only 2IgB7-H3 was detected in non-cancerous brain tissue, whereas 4IgB7-H3 was specific for GBM. 2IgB7-H3 expression was higher in GBM recurrences and increased resistance to temozolomide-mediated apoptosis. To conclude, 4IgB7-H3 is an interesting candidate for GBM targeted therapies, while 2IgB7-H3 could be involved in recurrence through resistance to chemotherapy.

Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

Oncogenic multidrug resistance (MDR) is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters. Drug efflux transporters, particularly the MDR P-glycoprotein ABCB1, represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets, but also for inhibiting apoptotic cell death cues, such as removal of proapoptotic signals. Several cell populations exhibiting the MDR phenotype co-exist within a tumor, such as cells forming the bulk tumor cell mass, cancer stem cells, and cancer persister cells. The key to regulation of ABCB1 expression is the cellular transcriptional machinery. Developmental signaling pathways (e.g, Hedgehog, Notch, Wnt/β-catenin, TGFβ, PITX2) are pivotal in governing cell proliferation, survival, differentiation and guiding cell migration during embryogenesis, and their reactivation during carcinogenesis, which is of particular significance for tumor initiation, progression, and metastasis, also leads to the upregulation of ABCB1. These pathways also drive and maintain cancer cell stemness, for which ABCB1 is used as a marker. In this review, the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.

IMMU-27. ANALYSIS OF IMMUNE SIGNATURES IN PEDIATRIC GLIOBLASTOMAS FOR PATIENT STRATIFICATION TO IMMUNOTHERAPY

BACKGROUNDPediatric glioblastoma (pGBM), despite being relatively rare (incidence rate: 0.5/100,000), are a leading cause of cancer deaths in children with a median overall survival of 9–15 months. In recent years, immunotherapy has emerged as one of the more promising advances in oncology, with impressive response rates reported in several malignancies. Effective application of immunotherapy in brain tumors depends upon a better understanding of the immune cell phenotype and mechanisms of immunosuppression in these tumors. This understanding will allow for the selection of patient population who are most likely to benefit from immunotherapeutic approaches.MATERIAL AND METHODSIn order to determine the frequency, distribution, and phenotype of tumor-infiltrating immune cells in pGBMs, we undertook an immunohistochemical survey on 19 recurrent pGBMs for CD3, CD8, CD4, CD163, PD-1, PD-L1, and FoxP3; RNA-Seq was also performed on a subset of 9 cases. Distribution of lymphocytes (LYMPHS) was recorded as intratumoral (IT) or perivascular (PV).RESULTSThe analysis indicates intratumoral CD3+ LYMPHS are commonly <5% of tumor cell mass; however, approximately half (10/19) of these recurrent pGBM have infiltrates that range from 5 to 30% CD3+ LYMPHS. Of these, 4/10 CD3+ tumors exhibit brisk CD8+ infiltrates that are associated with PD-L1+ tumor cells. These tumors with brisk CD3+/CD8+ LYMPHS and PD-L1+ tumor cells were associated with longer survivals. The data were confirmed by RNA-seq analysis.CONCLUSIONPD-L1+ pGBMs associated with CD3+/CD8+ LYMPH infiltrates deserve further investigation as candidates for immunotherapy.

Do adhesive molecules ICAM-1 and VCAM-1 affect the development and course of gastrointestinal tumors?

Solid tumors are composed of two compartments: cancerous cells constituting the essential mass of tumor and stromal tumor cells. Cell-cell and extracellular matrix-cell interactions are mediated by adhesive molecules (CAMs, cell adhesion molecules) and affect the growth, differentiation and migration of tumor cells. Abnormal ICAM expression may underlie in morphological disturbances, loss of cell-to-cell junctions, cytoskeleton disorganization, allowing cancer cells to detach from tumor mass and metastase. The aim of this work is to present the current state of knowledge and results of new research on the expression of selected adhesion molecules: ICAM-1 and VCAM-1 in patients with esophageal, gastric and colorectal cancer. Recently, the research of adhesion molecules in numerous cancers has been observed. It has been demonstrated that ICAM-1 participates in all stages of oncogenesis. The interaction of the host ICAM-1 with a ligand on a tumor cell and host cell during subsequent metastatic stages may become an attractive target for anticancer treatment. Studies have shown that VCAM-1 plays an important role in the process of tumor cell adhesion to endothelial cells and in the neovascularization process. The concentration of soluble VCAM-1 in serum correlates with the expression of VCAM-1 in tumor tissue, and is significantly reduced after surgical removal of the tumor. In this aspect sVCAM-1 can be treated as a sensitive diagnostic and prognostic marker.