abstract: Cancer stem cells and metastasis

Cancer stem cells and metastasis
Publication year: 2012

Seminars in Cancer Biology


Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in hematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

open access - PLoS ONE: Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer

"...We propose the side population of ascites from women with high-grade advanced stage papillary serous ovarian adenocarcinoma would be enriched for cancer stem-like cells, and would express a gene signature trend for “stemness” in ovarian cancer stem-like cells...."

"Ethics Statement
Fresh ascites was obtained from 10 women with high-grade advanced stage ovarian adenocarcinoma at the time of primary cytoreductive surgery at Brigham and Women's Hospital, Boston, MA......

".....In summary, an expression profile for SP enriched for cancer stem-like cells from ascites of ovarian cancer patients is reported. The nature of the “stemness” of the SP gene signature was demonstrated by the identification of several stem cell-related genes including an activated Notch signaling pathway. The results were biologically validated using identified SP population from human ovarian cancer cell lines. The SP gene list generated from ovarian cancer patients was also found to be enriched in recurrent tumors from ovarian cancer patients. These results have important implications concerning the tumor recurrence and potential therapeutic approach. The SP cells showed a dose dependent sensitivity towards Notch pathway inhibitor, suggests the Notch signaling pathway may be an important therapeutic target in ovarian cancer."

full free access: index - Cancer Stem Cells - special edition 2011 Journal of Oncology

Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma Open Access

Note: see Table 1 for cell types/stage included in study

".......None of the stem cell markers was expressed by all patients’ cells. No correlation with tumor type was demonstrated. The complexity of expression challenges the isolation of cancer stem cell."

full free access: Review Article: Cancer Stem Cells and Epithelial Ovarian Cancer

"This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer."