A cancer stem cell origin for human endometrial carcinoma?

Abstract

Endometrial cancer (EC) is the most common gynaecological malignancy affecting women in the western world. Cancer stem cells (CSCs) are defined as a subset of tumour cells with the capacity to self-renew and give rise to the differentiated cells that comprise the bulk of the tumour. Given that a rare population of epithelial stem/progenitor cells has been identified in human endometrium, it is possible that these cells or their progeny may be the source of the putative CSCs that may initiate and maintain EC. Studies have shown that some cells within EC have the capacity to initiate clones that undergo self-renewing cell division and form tumours in vivo that can be serially passaged, demonstrating self-renewal, proliferation and differentiation abilities of the potential EC stem cells (ECSCs). These potential ECSCs may be located within the tumour cell population expressing CD133 and/or within the side population. With the discovery of markers for ECSCs, it is hoped that ECSCs can be isolated and characterised, and that their role in the development of human EC will be further investigated. This knowledge opens the way for the development of new treatment modalities that target the CSCs, but spares normal endometrial stem/progenitor cells and other cells. Such treatments will be particularly useful for early-stage and pre-menopausal EC candidates where the uterus may be conserved, and for late-stage cases where hysterectomy is not curative and current treatments target the bulk tumour cells rather than CSCs.

Porcine uterus contains a population of mesenchymal stem cells

“…Indeed, since the first evidence for the existence of clonogenic cells in the human endometrium was provided by Chan et al (2004), several studies have reported the presence of a variety of stem-like cells in human and mouse uterus (Chan & Gargett 2006, Cervelló et al 2007, Kato et al 2007, Wolff et al 2007, Dimitrov et al 2008, Gargett et al 2009. Furthermore, emerging evidence indicates that some pathological conditions, such as endometrial cancer, endometriosis, and leiomyomata can be attributed to dysregulation of these same stem cells, or are derived from committed cells that acquire stem-like features (Sasson & Taylor 2008, Hubbard & Gargett 2010. Most studies on uterine stem cells have focused on human rather than mouse models, the latter being the only animal model studied until now.…”

Cancer Stem Cells in Tumor Heterogeneity

“…Similar studies in a wide variety of leukemias and solid tumors (AlHajj et al, 2003;Singh et al, 2004;Taylor et al, 2005;Patrawala et al, 2006;Hermann et al, 2007;O'Brien et al, 2007;Ricci-Vitiani et al, 2007;Eramo et al, 2008;Schatton et al, 2008), have followed to identify cell populations with an increased tumor-forming ability as compared to other populations from the same tumor. The interpretation of these and similar results has recently been somewhat complicated by the finding that the tumor formation efficiency of different cell populations can be greatly affected by the host animal, most notably by the level of immunodeficiency in recipient mice (Quintana et al, 2008) (Holland, 2001;Gerdes and Yuspa, 2005;Shupe and Petersen, 2005;Hubbard and Gargett, 2010;Sell, 2010;Waters et al, 2010;Visvader, 2011) (Jögi et al, 2002;Helczynska et al, 2003), or occur as a natural consequence of tumor progression (Delahunt, 1999), long before the cancer stem cell model regained mainstream interest in the research community.…”

Metastatic breast cancer cells in the bone marrow microenvironment: novel insights into oncoprotection

“…that equally affect all cells within a tumor [47]. The hierarchal model, on the other hand, holds that particular cells within a lineage are susceptible to transformation, and these self-renewing cells give rise to heterogeneous progeny [48, 49]. The cells at the pinnacle of the hierarchy can initiate de novo tumors and may account for resistance of cancer to chemotherapy and radiation [48, 49] (Fig.…”

“…These cells are expected to self-renew and give rise to new tumors limitlessly [48, 49]. The pluripotency marker Oct-4 is shown here as a potential marker of these cancer-initiating cells…”