No abstract

Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. To detect the prevalence of MMTV in Pakistani population, 666-bp-long MMTV envelop and 630-bp LTR sequences were amplified from breast cancer patient samples (tissue biopsies and peripheral blood) using mouse with mammary tumor as control. MMTV-like virus env and LTR DNA sequences were detected in 20 and 26 % of breast tumor samples, respectively, from the total of 80 breast cancer patients' blood and tissue samples. No significant association was observed between age, grade of disease, and lymph node involvement with the prevalence of MMTV-like sequences. Our data add to the growing number of studies implicating MMTV-like virus in human breast cancer, but still clear causal association of MMTV to breast cancer remains to be reputable.

Bone marrow stromal antigen 2 (BST-2) mediates various facets of cancer progression and metastasis. Here, we show that BST-2 is linked to poor survival in invasive breast cancer patients as its expression positively correlates with disease severity. However, the mechanisms that drive the pro‐metastatic functions of BST-2 are not fully understood. Correlation of BST-2 expression and tumor aggressiveness was analyzed in human tissue samples. Migration, invasion, and competitive experimental metastasis assays were used to measure the cellular responses after silencing BST-2 expression. Using a mouse model of breast cancer, we show that BST-2 promotes metastasis independent of the primary tumor. Additional experiments show that suppression of BST-2 renders non-adherent cancer cells non-viable by sensitizing cells to anoikis. Embedment of cancer cells in basement membrane matrix reveals that silencing BTS-2 expression inhibits invadopodia formation, extracellular matrix degradation, and subsequent cell invasion. Competitive experimental pulmonary metastasis shows that silencing BST-2 reduces the numbers of viable circulating tumor cells (CTCs) and decreases the efficiency of lung colonization. Our data define a previously unknown function for BST-2 in the i) formation of invadopodia, ii) degradation of extracellular matrix, and iii) protection of CTCs from hemodynamic stress. We believe that physical (tractional forces) and biochemical (ECM type/composition) cues may control BST-2’s role in cell survival and invadopodia formation. Collectively, our findings highlight BST-2 as a key factor that allows cancer cells to invade, survive in circulation, and at the metastatic site.