Metastasis Of Breast Carcinoma Research Articles

Proteomic analysis of O-GlcNAcylated proteins in invasive ductal breast carcinomas with and without lymph node metastasis

The potential role of protein O-GlcNAcylation in cancer has been studied extensively, and the spread of cancer cells to regional lymph nodes is the first step in the dissemination of breast cancer. However, the correlation between O-GlcNAcylation and lymphatic metastasis in breast cancer remains elusive. In this study, we demonstrated that the overall O-GlcNAcylation as well as O-GlcNAc transferase (OGT) tends to decrease in response to the augmentation of lymph node metastasis (LNM) in invasive ductal breast carcinomas (IDCs). Although accumulating evidence indicates that individual O-GlcNAcylation may be important in the pathogenesis of breast cancer, O-GlcNAcylated proteins in IDCs are still largely unexplored. Herein, O-GlcNAcylated proteins of IDCs were chemo-enzymatically enriched and identified via liquid chromatography combined with tandem mass spectrometry. In total, 155 O-GlcNAcylated proteins were determined, of which 41 were only observed in LNM tissues, while 40 were unique in non-LNM samples. Gene ontology analysis showed that O-GlcNAc is primarily a nucleocytoplasmic post-translational modification, and most enriched functional terms were related to cancer development in both metastatic and non-metastatic IDCs. Moreover, several O-GlcNAcylated proteins involved in glycolysis and its accessory pathway were identified from LNM and non-LNM groups, respectively. These results indicate that the O-GlcNAcylation statuses of individual proteins were independent of the overall O-GlcNAcylation levels of metastatic and non-metastatic IDCs. Aberrant O-GlcNAc modification of these proteins might be associated with LNM progression.

Metastasis of Breast Carcinoma to the External Auditory Canal: Report of an Unusual Case and Literature Review.

We present a case of metastasis of the external auditory canal (EAC) from a primary breast carcinoma in a 53-year-old female with a review of the literature. The patient had been diagnosed with a primary carcinoma 4 years previously. The metastasis had developed recently in her left EAC and presented as a bulky, fleshy, bleeding mass. The mass was causing hearing loss on the left due to complete obstruction in the left EAC. The mass was incompletely removed with a surgical operation and histopathologically metastasis was proven. Although there are few case reports in the literature of various cancers metastasizing to the EAC, metastasis in the EAC from the breast carcinoma is exceedingly rare and only one case has been reported in the literature so far.

Breast carcinoma metastasis suppressor gene 1 (BRMS1): update on its role as the suppressor of cancer metastases.

BRMS1 was discovered over a decade ago as a potential tumor suppressor gene. In this review, we summarize the recent findings about the structure of BRMS1, mechanisms of its action and a role of BRMS1 in the cancer progression. As a suppressor of metastasis, BRMS1 has demonstrated a variety of ways to act on the cell functions, such as cell migration, invasiveness, angiogenesis, cell survival, cytoskeleton rearrangements, cell adhesion, and immune recognition. This variety of effects is a likely reason behind the robustness of anti-metastatic influence of BRMS1. Intracellular signaling mechanisms employed by BRMS1 include regulation of transcription, EGF/HER2 signaling, and expression of NF-kB, fascin, osteopontin, and IL-6. Recently reported clinical studies confirm that BRMS1 can indeed be used as a prognostic marker. Approaches to employ BRMS1 in a development of anti-cancer treatment have also been made. The studies reviewed here with respect to BRMS1 structure, cellular effects, intracellular signaling, and clinical value consolidate the importance of BRMS1 in the development of metastasis.

The LPA1/ZEB1/miR-21-activation pathway regulates metastasis in basal breast cancer.

Lysophosphatidic acid (LPA) is a bioactive lipid promoting cancer metastasis. LPA activates a series of six G protein-coupled receptors (LPA1-6). While blockage of LPA1in vivo inhibits breast carcinoma metastasis, down-stream genes mediating LPA-induced metastasis have not been yet identified. Herein we showed by analyzing publicly available expression data from 1488 human primary breast tumors that the gene encoding the transcription factor ZEB1 was the most correlated with LPAR1 encoding LPA1. This correlation was most prominent in basal primary breast carcinomas and restricted to cell lines of basal subtypes. Functional experiments in three different basal cell lines revealed that LPA-induced ZEB1 expression was regulated by the LPA1/Phosphatidylinositol-3-Kinase (Pi3K) axis. DNA microarray and real-time PCR analyses further demonstrated that LPA up-regulated the oncomiR miR-21 through an LPA1/Pi3K/ZEB1-dependent mechanism. Strikingly, treatment with a mirVana miR-21 inhibitor, or silencing LPA1 or ZEB1 completely blocked LPA-induced cell migration in vitro, invasion and tumor cell bone colonization in vivo, which can be restored with a mirVana miR-21 mimic. Finally, high LPAR1 expression in basal breast tumors predicted worse lung-metastasis-free survival. Collectively, our results elucidate a new molecular pathway driving LPA-induced metastasis, thus underscoring the therapeutic potential of targeting LPA1 in patients with basal breast carcinomas.

DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses breast carcinoma metastasis.

Epithelial–mesenchymal transition (EMT) has a major role in cancer progression and metastasis. However, the specific mechanism of transcriptional repression involved in this process remains largely unknown. Dachshund homologue 1 (DACH1) expression is lost in invasive breast cancer with poor prognosis, and the role of DACH1 in regulating breast cancer metastasis is poorly understood. In this study, significant correlation between the expression of DACH1 and the morphology of breast cancer cells was observed. Subsequent investigation into the relationship between DACH1 and EMT showed that overexpression of DACH1 in ZR-75-30 cells induced a shift towards epithelial morphology and cell–cell adhesion, as well as increased the expression of the epithelial marker E-cadherin and suppressed cell migration and invasion. In contrast, silencing DACH1 in MCF-7 and T47D cells disrupted the epithelial morphology and cell–cell contact, reduced the expression of E-cadherin, and induced cell migration and invasion. DACH1 also specifically interacted with SNAI1, but not SNAI2, to form a complex, which could bind to the E-box on the E-cadherin promoter in an SNAI1-dependent manner. DACH1 inhibited the transcriptional activity of SNAI1, leading to the activation of E-cadherin in breast cancer cells. Furthermore, the level of DACH1 also correlated with the extent of metastasis in a mouse model. DACH1 overexpression significantly decreased the metastasis and growth of 4T1/Luc cells in BALB/c mice. Analysis of tissue samples taken from human breast cancers showed a significant correlation between the expression of DACH1 and E-cadherin in SNAI1-positive breast cancer. Collectively, our data identified a new mechanistic pathway for the regulation of EMT and metastasis of breast cancer cells, one that is based on the regulation of E-cadherin expression by direct DACH1–SNAI1 interaction.

Activation of neuroimmune pathways increases therapeutic effects of radiotherapy on poorly differentiated breast carcinoma.

Recent studies document the importance of neuronal dysfunction in cancer development and metastasis. We reported previously that both depletion of neuropeptides in capsaicin-sensitive sensory nerve endings and vagotomy increases metastasis of triple negative breast carcinoma. Of the sensory neuropeptides, Substance P (SP) is distributed widely for regulation of immune functions. We therefore examined the affects of continuous exposure to low doses of SP on brain metastatic cells of the mouse breast carcinoma (4TBM) in the presence of radiotherapy (RT) thought to increase antigenicity of cancer cells. 4TBM cells have a cancer stem cell phenotype and induce extensive visceral metastasis after orthotopic inoculation into the mammary pad. Results demonstrated that SP treatment decreases the number of tumor-infiltrating myeloid-derived suppressor cells as well as the TNF-α response to LPS challenge. SP also increased CD4+Cd25(bright) cells in draining lymph nodes of tumor-bearing animals and IFN-γ secretion from leukocyte culture prepared from lymph nodes and spleens of tumor-bearing animals. SP also prevented tumor-induced degeneration of sensory nerve endings and altered release of angiogenic factors from cancer-associated fibroblasts (CAF) and tumor explants. In accordance with these observed immunological effects, combination treatment of continuous SP with a single dose of RT induced complete tumor regression and significantly reduced or prevented metastasis in 50% of the animals while suppressing primary tumor growth and metastasis in the remaining mice. These original findings demonstrate that SP through neuroimmune modulation can prevent formation of immune suppression in the tumor microenvironment, enhance cytotoxic immunity in the presence of RT and prevent metastatic growth.

The Evaluation of Primary Lesion and Axillary Metastasis in Breast Carcinoma By 18F-FDG PET/CT

The Evaluation of Primary Lesion and Axillary Metastasis in Breast Carcinoma By 18F-FDG PET/CT

Study of Metastasis in Lymphnode Biopsies with Special Reference to Immunohistochemistry (IHC) in Metastatic Breast Carcinoma.

Lymph nodes are the most common site of metastatic malignancy, and sometimes constitute the first clinical manifestation of the disease. Metastases are tumour implants discontinuous with the primary tumour. The characterization of a neoplasm as primary or metastatic has always troubled surgical pathologists. To study distribution of lymph node metastasis in North Karnataka region based on age, sex, location and morphological features, and to explore the utility of special stains and immunohistochemistry (IHC) in its diagnosis. The present study includes 228 cases of lymph node metastasis studied over a 10-year period (July 2004- June 2014). The H&E slides were reviewed, special stains and IHC done wherever necessary. Out of 228 cases, maximum were seen between 2012-2014 (79 cases; 34.65%). Age ranged from 16-85y (Mean- 47.02) with female predominance (Male:Female 1:2.55.). In 186 cases (81.58%) more than one lymph node received, while in majority of cases (35.09%) size of the lymph node was between 1-2cms. Most common site of metastasis was axillary lymph nodes (33.77%) followed by cervical (22.50%) and pelvic (9.64%). Primary was mainly from breast carcinoma (33.77%) followed by squamous cell carcinoma (31.57%) and adenocarcinoma (10.52%). IHC in 60 cases with breast carcinoma metastasis showed ER positivity in 45.00%, PR positivity in 41.67% and HER2/neu positivity in 38.33%. Identification of the size, number, microscopic type and possible primary site of metastasis is important prognostically especially in breast carcinoma. This study elaborates the pattern of distribution of lymph node metastasis in North Karnataka region with IHC as an aid to diagnosis.

Surgical vertebral body cementoplasty as spinal cancer metastasis management

Spinal metastases of cancer are frequent and their treatment strategy remains a problem. The aim of the present paper is to present the technique of cementoplasty and its originality. Spine corporeal cementoplasty techniques were performed in 9 patients with spine metastasis treated at Neurosurgery Department between 2002 and 2005. This series is composed of four women and five men. The average age of patients was 54 years. All patients were admitted for treatment of metastasis of breast carcinoma, metastasis of breast adenocarcinoma (three cases), colon cancer (two cases), pulmonary adenocarcinoma (one case) and melanoma (three cases). Metastasis was located on the cervical spine (3 cases), thoracic spine (4 cases) and lumbar spine (2 cases).No case of cement leaking was observed. In eight patients neurological deficit and pain were decreased. In one patient we noted a persistence of neurological deficit but pain decreased. A post-operative radiological analysis showed good spine stability. Before their death this treatment had improved their quality of life.The technique of surgical cementoplasty described in this paper may be used for a surgical treatment of metastasis and spinal stabilisation. It is an alternative to a palliative treatment of metastasis when it is not possible to perform vertebroplasty.

Pathological Spinal Fracture Due to Metastasis of Mucinous Breast Carcinoma

Summary Spinal metastases represent a common event in oncological patient. Such tumour spread can reduce the life quality significantly due to pain, pathological fracture and spinal cord compression. Breast cancer is among the most common primary sources. However, certain histological types of breast cancer, including mucinous carcinoma, are known for less aggressive behaviour. Here we present a clinical case of 44-year-old female affected by mucinous carcinoma in left mammary gland, resulting in regional lymph node involvement and multiple remote metastases in left lung and Th7 vertebra. This case is notable as mucinous breast carcinoma rarely develops at such age and infrequently shows wide metastatic spread.

RETRACTED: Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma

The present study deals with the molecular mechanisms involved in the regulation of E-cadherin expression under hypoxia, because the adjustment of the amount of E-cadherin due to physical stimuli of the microenvironment might influence the colonization of metastasis to skeleton. We analyzed the effect of 1% oxygen tension, that is similar to that encountered in the bone marrow by metastatic cells spreading from breast carcinoma. The purpose was to evaluate the hypoxia-orchestrated control of E-cadherin transactivation via hypoxia inducible factor-1 (HIF-1) and peroxisome proliferator activated receptor-γ (PPARγ), and the involvement of Hippo pathway members, as regulators of transcription factors. To give a translational significance to the study, we took into consideration human pair-matched ductal breast carcinoma and bone metastasis: E-cadherin and Wwox were expressed in bone metastasis but not in breast carcinoma, while HIF-1α and TAZ seemed localized principally in nuclei of metastasis and were found in all cell compartments of breast carcinoma. A close examination of the regulatory mechanisms underlying E-cadherin expression in bone metastasis was done in 1833 clone derived from MDA-MB231 cells. Hypoxia induced E-cadherin only in 1833 clone, but not in parental cells, through HIF-1 and PPARγ activities, while Wwox decreased. Since Wwox was highly expressed in bone metastasis, the effect of ectopic Wwox was evaluated, and we showed E-cadherin transactivation and enhanced invasiveness in WWOX transfected 1833 cells. Also, hypoxia was additive with ectopic Wwox remarkably enhancing HIF-1α nuclear shuttle and accumulation due to the lengthening of the half-life of HIF-1α protein; under this experimental condition HIF-1α appeared as a slower migrated band compared with control, in agreement with the phosphorylation state. The in vitro data strongly supported the almost exclusive presence of HIF-1α in nuclei of human-bone metastasis. Thus, we identified Wwox as a novel molecule in the HIF-1α-HDM2 regulatory loop, necessary for the dynamic regulation of the HIF-1α amount, and we suggested that the reduction of endogenous Wwox free pool under hypoxia might also be due to the interaction with HDM2, sequestering the E3 ubiquitin ligase. We highlighted the importance of nuclear HIF-1α in the biology of metastasis for the mesenchymal-epithelial transition: this phenotype was regulated by Wwox plus hypoxia through E-cadherin target gene, playing a pivotal role in bone metastasis colonization.

Novel alternatively spliced isoform of synuclein gamma

Introduction: Since Synuclein γ (SNCG) is found highly expressed in advanced breast cancer it was initially described as breast-cancer specific gene (BCSG1). Clinical studies demonstrate the correlation of high SNCG expression with advanced stages, metastasis and poor prognosis in breast and ovarian carcinomas, i.e. reduced relapse-free and overall survival periods. In vitro analyses revealed a SNCG-dependent stimulation of ligand-dependent transcriptional activity of ERα. So far, four mRNA isoforms of SNCG were described, but only isoforms-1 and -2 code for active proteins. For the first time, we analyzed expression levels of SNCG mRNA isoforms in regard to hypoxia or acidosis, in vitro in endometrial cancer cells.

Absence of multiple atypical chemokine binders (ACBs) and the presence of VEGF and MMP-9 predict axillary lymph node metastasis in early breast carcinomas.

The aim of this study was to determine the frequency of axillary lymph node (ALN) metastasis of early breast cancers by evaluating the status of DARC, D6 and CCX-CKR and the levels of VEGF and MMP-9. The status of DARC, D6 and CCX-CKR and the levels VEGF and MMP-9 were evaluated in ALN- (n = 130) and ALN + (n = 88) patients with T1 breast cancer by immunohistochemical staining. For ALN, likelihood ratio χ (2)-tests were used for univariate analysis and logistic regression for multivariate analysis. Univariate analysis identified the nuclear grade, VEGF and MMP-9 expression and absence of DARC, D6 and CCX-CKR as predictors of ALN involvement. When combining the three receptors (DARC, D6 and CCX-CKR) together, tumors with multiple absence (multi-absence, any two or three loss) had a higher likelihood of being ALN positive than non-multi-absence (coexpression of any two or three) tumors (56.2 vs. 27.9 %, P < 0.001). The final multivariate logistic regression revealed nuclear grade, VEGF, MMP-9 and non-multi-absence versus multi-absence to be independent predictors of ALN involvement; the odds ratio (OR) and 95 % CI for non-multi-absence tumors versus multi-absence were 0.469 (0.233-0.943). Multi-absence was also associated with the involvement of four or more lymph nodes among ALN + tumors. Moreover, tumors with multi-absence had higher VEGF (78.1 vs. 50.0 %, P < 0.001) and MMP-9 (81.3 vs. 36.1 %, P < 0.001) expression than non-multi-absence tumors. Our data highlight that the absence of DARC, D6 and CCX-CKR in combination, which is associated with higher VEGF and MMP-9 expression, predicts the presence and extent of ALN metastasis in breast cancer.

Prospect and guideline update of sentinel lymph node biopsy for patients with early-stage breast carcinoma

Axillary lymph nodes are the most common and initial site of metastasis of breast carcinoma. Precise axillary staging of breast carcinoma before initial treatment is crucial as it allows efficient identification for local and systemic treatment options, and provides prognostic information. Sentinel lymph node biopsy (SLNB) is an accurate minimally invasive technology for axillary staging. Although top evidence of high-quality clinical trials showed that SLNB could safely and effectively replace axillary lymph node dissection (ALND) for axillary negative patients with decrease in complications and improvement in quality of life, there are specific indications and contraindications for SLNB. Clinicians should balance the compliance of guideline and native clinical practice, especially for the circumstance of multifocal/multicentric lesion, breast biopsy history, and neoadjuvant chemotherapy. With the accumulation of clinical practice and new results of clinical trials, axillary therapy has changed from unique surgery to patient-tailored multi-disciplinary intervention, although ALND should be recommended traditionally if SLNB is positive. Intensive and accurate preoperative axillary staging is gradually valued by clinicians. Development of imaging modality especially ultrasonography and ultrasound-guided biopsy can identify some extra lymph node positive patients directly to ALND with avoidance of unnecessary SLNB. Thus, the positive rate of SLNB will decline significantly. It seems possible that axillary management will step into a noninvasive era abandoning SLNB in some patients with small breast cancer. In this article we review the prospect and guideline update of SLNB for patients with early-stage breast cancer.

Bayesian variable selection and modelling for metastatic breast cancer data

A Bayesian model selection procedure is applied to data on 90 women with metastatic breast cancer. Protein covariates are measured on nucleus, cytoplasm, membrane, and stroma of primary breast carcinoma and lymph node metastasis tissue. Multiple imputation is performed to deal with missing data. Zellner's g-prior is used in the Bayesian variable selection procedure. The model space is reduced using posterior variable inclusion probabilities, and then posterior model probabilities are used to derive a candidate set of models. Bayesian model averaging is employed to robustly estimate survival time, and the goodness of fit of the derived model assessed by the correlation between estimated and observed survival times. The results show evidence of proteins having different rules in different parts of the tissue cell with respect to patient survival. Therefore, a recommendation is given on which part of the cell to observe certain proteins for prognosis. The models obtained are robust toward censoring and showed correlations between the observed and the predicted data between 0.7 and 0.84. References J. Adams, P. J. Carder, S. Downey, M. A. Forbes, K. MacLennan, V. Allgar, S. Kaufman, S. Hallam, R. Bicknell, J. J. Walker, F. Cairnduff, P. J. Selby, T. J. Perren, M. Lansdown, and R. E. Banks. Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res., 60(11):2898–2905, 2000. http://cancerres.aacrjournals.org/content/60/11/2898 . F. Bray, J.-S. Ren, E. Masuyer, and J. Ferlay. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int. J. Cancer, 132(5):1133–1145, 2013. doi:10.1002/ijc.27711 . M. Clyde and E. I. George. Model uncertainty. Stat. Sci., 19(1):81–94, 2004. http://projecteuclid.org/download/pdfview_1/euclid.ss/1089808274 . A. R. T. Donders, G. J. M. G. van der Heijden, T. Stijnen, and K. G. M. Moons. Review: a gentle introduction to imputation of missing values. J. Clin. Epidemiol., 59(10):1087–1091, 2006. doi:10.1016/j.jclinepi.2006.01.014 . J. Ferlay, I. Soerjomataram, D. F. M. Ervik, F. Bray, R. Dikshit, S. Elser, C. Mathers, M. Rebelo, and D. M. Parkin. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer, World Health Organization, 2014. http://globocan.iarc.fr . E. I. George and R. E. McCulloch. Variable selection via Gibbs sampling. J. Am. Stat. Assoc., 88(423):881–889, 1993. doi:10.1080/01621459.1993.10476353 . E. I. George and R. E. McCulloch. Approaches for Bayesian variable selection. Stat. Sinica, 7(2):339–373, 1997. http://www3.stat.sinica.edu.tw/statistica/j7n2/j7n26/j7n26.htm . J. Geweke. Variable selection and model comparison in regression, volume 5 of Bayesian statistics, pages 609–620. Oxford University Press, 1996. J. A. Hoeting, D. Madigan, A. E. Raftery, and C. T. Volinsky. Bayesian model averaging: a tutorial. Stat. Sci., 14(4):382–401, 1999. http://www.jstor.org/stable/2676803 . D. G. Kleinbaum and M. Klein. Survival Analysis: A self-learning text. Statistics for Biology and Health. New York, Springer-Verlag, 2011. doi:10.1007/0-387-29150-4 . E. E. Leamer. Regression selection strategies and revealed priors. J. Am. Stat. Assoc., 73(363):580–587, 1978. doi:10.1080/01621459.1978.10480058 . E. E. Leamer. Specification searches: Ad hoc inference with nonexperimental data. Wiley New York, 1978. S. Mallett, P. Royston, R. Waters, S. Dutton, and D. G. Altman. Reporting performance of prognostic models in cancer: a review. BMC Med., 8(1):21, 2010. doi:10.1186/1741-7015-8-21 . H. C. McCosker. Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients. PhD thesis, School of Biomedical Sciences, QUT, 2012. http://eprints.qut.edu.au/53580/ . T. J. Mitchell and J. J. Beauchamp. Bayesian variable selection in linear regression. J. Am. Stat. Assoc., 83(404):1023–1032, 1988. doi:10.1080/01621459.1988.10478694 . K. Pantel and R. H. Brakenhoff. Dissecting the metastatic cascade. Nat. Rev. Cancer, 4(6):448–456, 2004. doi:10.1038/nrc1370 . R. Radpour, Z. Barekati, C. Kohler, W. Holzgreve, and X. Y. Zhong. New trends in molecular biomarker discovery for breast cancer. Genet. Test. Mol. Bioma., 13(5):565–571, 2009. doi:10.1089/gtmb.2009.0060 . A. E. Raftery, D. Madigan, and J. A. Hoeting. Bayesian model averaging for linear regression models. J. Am. Stat. Assoc., 92(437):179–191, 1997. doi:10.1080/01621459.1997.10473615 . A. Zellner. On assessing prior distributions and Bayesian regression analysis with g-prior distributions, volume 6 of Bayesian inference and decision techniques: Essays in Honor of Bruno De Finetti, pages 233–243. North-Holland, Amsterdam, The Netherlands, 1986. A. Zellner. An introduction to Bayesian inference in econometrics. New York: John Wiley and Sons, 1996.

Metastasis of Breast Carcinoma to the Maxillary Sinus

Metastasis of Breast Carcinoma to the Maxillary Sinus

Zosteriform cutaneous metastasis of breast carcinoma in a male patient

Zosteriform cutaneous metastasis of breast carcinoma in a male patient

α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma

Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, α-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with α-parvin expression. Twenty-one (37.5 %) ILCs stained positive for α-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). α-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. α-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that α-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.

Integrin α3β1 Can Function to Promote Spontaneous Metastasis and Lung Colonization of Invasive Breast Carcinoma

Significant evidence implicates α3β1 integrin in promoting breast cancer tumorigenesis and metastasis-associated cell behaviors in vitro and in vivo. However, the extent to which α3β1 is actually required for breast cancer metastasis remains to be determined. We used RNA interference to silence α3 integrin expression by approximately 70% in 4T1 murine mammary carcinoma cells, a model of aggressive, metastatic breast cancer. Loss of α3 integrin reduced adhesion, spreading, and proliferation on laminin isoforms, and modestly reduced the growth of orthotopically implanted cells. However, spontaneous metastasis to lung was strikingly curtailed. Experimental lung colonization after tail vein injection revealed a similar loss of metastatic capacity for the α3-silenced (α3si) cells, suggesting that critical, α3-dependent events at the metastatic site could account for much of α3β1's contribution to metastasis in this model. Reexpressing α3 in the α3si cells reversed the loss of metastatic capacity, and silencing another target, the small GTPase RhoC, had no effect, supporting the specificity of the effect of silencing α3. Parental, α3si, and α3-rescued cells, all secreted abundant laminin α5 (LAMA5), an α3β1 integrin ligand, suggesting that loss of α3 integrin might disrupt an autocrine loop that could function to sustain metastatic growth. Analysis of human breast cancer cases revealed reduced survival in cases where α3 integrin and LAMA5 are both overexpressed. α3 integrin or downstream effectors may be potential therapeutic targets in disseminated breast cancers, especially when laminin α5 or other α3 integrin ligands are also over-expressed.

Spinal intramedullary metastasis of breast cancer.

Objective. Breast cancer accounts for approximately one-third of all cancers in females. Approximately 8.5 % of all central nervous system metastases are located in the spinal cord. These patients have rapidly progressing neurological deficits and require immediate examination. The aim of surgery is decompression of neural tissue and histological evaluation of the tumor. In this paper, we present a case of breast cancer metastasis in thoracic spinal intramedullary area which had been partially excised and then given adjuvant radiotherapy. Case. A 43-year-old female patient with breast cancer for 8 years was admitted to our hospital with complaints of weakness in both legs. Eight years ago, she received chemotherapy and radiotherapy. On her neurological examination, she had paraparesis (left lower extremity: 2/5, right lower extremity: 3/5) and urinary incontinence. Spinal MRI revealed a gadolinium enhancing intramedullary lesion. Pathologic examination of the lesion was consistent with breast carcinoma metastasis. The patient has been taken into radiotherapy. Conclusion. Spinal intramedullary metastasis of breast cancer is an extremely rare situation, but it has a high morbidity and mortality rate. Microsurgical resection is necessary for preservation or amelioration of neurological state and also for increased life expectancy and quality.