Lack of correlation of stem cell markers in breast cancer stem cells

Abstract

Background:Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial.Methods:We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy.Results:CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate.Conclusions:Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer.

Induced Expression of Cancer Stem Cell Markers ALDH1A3 and Sox-2 in Hierarchical Reconstitution of Apoptosis-resistant Human Breast Cancer Cells

“…By contrast, progenitor cells are proliferative and divide rapidly [21, 40]. In the previous report, ALDH1 expression was found in non-proliferating Ki-67 − cancer cells, and proliferating cancer cells were ALDH1 − [32], which is not consistent with our results that the majority of ALDH1A3 + cells were Ki-67 + .…”

“…CSCs are defined as having both the ability to self-renew and to differentiate into mature cells, and are thought to have resistance to chemotherapy and radiotherapy [4, 8, 19, 37]. Hierarchical cellular structures of breast tumors are organize by stem cells, that CSCs give rise to rapidly dividing progenitor cells, and mature cells [9, 21]. …”

mTOR inhibitors counteract tamoxifen-induced activation of breast cancer stem cells

“…As published before, we confirm that CSCs are ER negative and this phenotype is independent of the primary tumor ER-status [62]. Hence, mTOR activation by tamoxifen might not depend on the ER status but is instead induced through other signaling cascades in CSCs.…”

Targeting highly expressed extracellular HSP90 in breast cancer stem cells inhibits tumor growthin vitroandin vivo

“…Besides the CD44 C /CD24 ¡/low molecular phenotype, various studies have identified several other BCSC markers such as aldehyde dehydrogenase 1 (ALDH1), CD133, Sox2, CK5, a-6integrin/CD49f, b-1 integrin/CD29, and lack of estrogen receptor (ER). 14 At the time of detection, most solid tumors are already genetically altered, and tend to resist therapies that target a single molecular determinant. 15 Thus, a simultaneous attack on multiple nodes of a cancer cell web of overlapping signaling pathways should be more likely to affect survival than inhibition of one or even a few individual signaling nodes.…”