Alpha‐6 integrin is necessary for the tumourigenicity of a stem cell‐like subpopulation within the MCF7 breast cancer cell line

Abstract

The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic subpopulation of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This subpopulation is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule a6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows a6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells. ' 2007 Wiley-Liss, Inc.

Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

“…Based on the above results, we analyzed the functional role of GD2 and GD3 and the involved GTs for their biosynthesis, B4GALNT1 and ST8SIA1, which were also up-regulated in CSCs. The human breast cancer cell line MCF7, which was reported to contain a subpopulation CD44 hi CD24 lo cells with features of stem cells (50,51) and expressed GD2 and GD3 at a satisfactory level as shown in this study, was used in knockdown experiments with a lentiviral-based shRNA expression vector, because it was difficult to transfect HMLE-Twist-ER cells efficiently enough for functional assays, mammosphere formation, and cell motility activity. At the mRNA level, we observed 82% and 51% suppression for ST8SIA1 and B4GALNT1, respectively (Fig.…”

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

“…Although the CD29/CD49f integrins have been implicated in the function of BCSCs and other CSCs (81,82,93), much needs to be learned about the contribution of these integrins to the genesis of BCSCs. It has been shown that CD49f and CD29 contribute to therapy resistance, tumor relapse and metastasis in breast cancer.…”

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression

“…Since then, several techniques have been established to isolate or enrich for tumorigenic breast cancer stem cells (BCSCs), including side-population (SP) separation and mammosphere culture (6,7). In breast cancer, the mammosphere culture system has been widely used to identify and enrich for putative stem cells using breast cancer cell lines (8). In a previous study, we described an in vitro culture system to propagate primary human mammary epithelial stem cells and progenitor cells in an undifferentiated state based on their ability to proliferate in suspension as spherical structures when cultured on non-adherent surfaces in the presence of growth factors.…”