Molecular definition of breast tumor heterogeneity.

By M. Shipitsin, Lauren L. Campbell, P. Argani, S. Weremowicz, Noga Bloushtain-Qimron, Jun Yao, T. Nikolskaya, T. Serebryiskaya, Rameen Beroukhim, Min Hu and 11 more. Cancer Cell, 2007

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Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/5a7dc5e6c008610cd2a47c17460b549ee0c36b6c

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Citations in the corpus

The epithelial-mesenchymal transition generates cells with properties of stem cells. (2008, positive): “…CD24low cells and CD44low/CD24high cells from three normal reduction mammoplasty tissues and from five neoplastic human breast tissues and carried out serial analysis of gene expression (SAGE)—an alternative method of gauging the spectrum of mRNAs expressed within tissues (Shipitsin et al., 2007).”
TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. (2008, neutral): “Several activities have been ascribed to TGFβ that would favor tumor progression in general, including the maintenance of a mesenchymal phenotype (Shipitsin et al., 2007) or the dampening of immune functions (Gorelik and Flavell, 2002).”
Identification of selective inhibitors of cancer stem cells by high-throughput screening (2009, methodology): “, 2003), and (3) CD44+ versus CD24+ normal and neoplastic primary human mammary epithelial cells (Shipitsin et al., 2007).”
let-7 regulates self renewal and tumorigenicity of breast cancer cells. (2007, background): “…considered in light of evidence for possible phenotypic heterogeneity of T-IC, as recently suggested for glioma (Beier et al., 2007) and of the heterogeneity of breast tumor cells that develop after tumor initiation secondary to additional mutations or epigenetic changes (Shipitsin et al., 2007).”
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. (2014, background): “…Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands 8Co-first author 9Present address: Netherlands Cancer Institute, Division of Molecular Pathology, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands *Correspondence: andyminn@exchange.upenn.edu http://dx.doi.org/10.1016/j.cell.2014.09.051”
Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition (2008, result): “These findings are consistent with the recent observation that CD24(2) cells isolated from breast cancer tissues display a mesenchymal phenotype attributable to the activation of TGFb and Wnt signaling [30], two pathways known to be involved in EMT [31].”
The therapeutic promise of the cancer stem cell concept. (2010, background): “breast cancer cells and found no correlation between CD24 and/or CD44 expression in primary invasive breast carcinomas with any specific tumor characteristics (42).”
The properties of high-dimensional data spaces: implications for exploring gene and protein expression data (2008, background): “Furthermore, heterogeneity may also arise within the tumour cell population itself from the differentiation of cancer stem cells, the molecular profiles of which are the focus of considerable interes”
Modelling breast cancer: one size does not fit all (2007, background): “Is the expression of CD44 + CD24 − ESA + markers broadly indicative of tumour-initiating subpopulations within cell lines? Accumulating evidence suggests that their expression is heterogeneous within cell lines and breast cancer”
Cancer stem cells in solid tumours: accumulating evidence and unresolved questions (2008, background): “By contrast, an increased number of CD24 + cells has been reported in distant metastases in breast cancer patients despite the CD44 + basal cell signature predicting decreased patient survival and a higher risk of distant metastases in lymph node-negative patients with invasive breast cance”
Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy (2008, background): “Disregarding the stromal, endothelial, and hematopoietic elements recruited and incorporated into the tumor, it has been suggested that TG and NTG populations arise from different cells and not from a single CSC [9].”