Functional and molecular characterisation of mammary side population cells

Abstract

Background: Breast cancer is thought to arise in mammary epithelial stem cells. However, the identity of these stem cells is unknown. Methods:Studies in the haematopoetic and muscle systems show that stem cells have the ability to efflux the dye Hoechst 33342. Cells with this phenotype are referred to as the side population (SP). We have adapted the techniques from the haematopoetic and muscle systems to look for a mammary epithelial SP. Results:Of mammary epithelial cells isolated from both the human and mouse mammary epithelia, 0.2-0.45% formed a distinct SP. The SP was relatively undifferentiated but grew as typical differentiated epithelial clones when cultured. Transplantation of murine SP cells at limiting dilution into cleared mammary fat pads generated epithelial ductal and lobuloalveolar structures.Conclusion: These data demonstrate the existence of an undifferentiated SP in human and murine mammary epithelium. Purified SP cells are a live single-cell population that retain the ability to differentiate in vitro and in vivo. Studies of haematopoetic cells have suggested that the SP phenotype constitutes a universal stem cell marker. This work therefore has implications for mammary stem cell biology.

RETRACTED ARTICLE: Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

“…Cancer stem cell (CSC) hypothesis has received more and more attention in recent times for its better explanation of the initiation of relapse and metastasis in several types of carcinomas including gastric carcinoma (Reya et al, 2001;Houghton et al, 2004;McDonald et al, 2008). In recent research, several malignant tumor tissues and cell lines have been discovered to possess CSCs, and include acute lymphoblastic leukemia and several solid tumors like breast, colon, hepatic, prostate, lung, and gastric cancers (Alvi et al, 2003;Chiba et al, 2006;Ho et al, 2007;Ricci-Vitiani et al, 2007;Fukuda et al, 2009;Oates et al, 2009). This has strengthened the hypothesis that the initiation of relapse and metastasis may be caused by CSCs.…”

Attributes of adult stem cells

“…These cells are bipotential, giving rise to luminal and myoepithelial cells [127,128]. In murine mammary glands the SP fraction is enriched for stem cells, determined by the proportion of LRCs and the ability to repopulate 'cleared' (indigenous epithelial cells removed to allow engraftment of transplanted cells) mammary fat pads in vivo with both myoepithelial and luminal lineages [129]. In fact, single cells expressing either CD49f (α6-integrin) or CD29 (β1-integrin) can accomplish this [130,131].…”

Neosis: A Novel Type of Cell Division in Cancer

“…2H-O), unlike the characteristic of SP (side population) cells enriched for stem cell activity. 33 Protrusion of the nuclear envelope is probably initiated by microtubule-mediated chromatin mobility, 34 resulting in the nuclear bud into which the neotic daughter genome is transported; asymmetric cytokinetic cleavage around the nuclear bud (Fig. 6C) results in the detachment of Raju cell from NMC.…”

“…2) the stem cell property of Hoechst dye efflux. 33 The perpetuation of tumor-initiating Raju cells, which mature into aging, heterogeneous tumor cell population (Fig. 7), appears to occur several times nonsynchronously and parasexually via polyploidisation and S/T neotic divisions interspersed by extended MLS through tumor progression.…”