Dr. Weeks’ Comment: The tumor – be it in the brain or the colon or the liver or lung is the consequence of cancer and not the cancer itself. The tumor is the symptom of the metabolic disruption which we call cancer. Professor Tom Seyfried at Boston College has long taught that cancer is a metabolic process and that the tumor is not the appropriate target.
Oncogenes are notsignificant since they are symptoms of cytosomal and mitochondrial cancer metabolic processes and not causative. Cancer as a Mitchondrial Metabolic Disease by Prof. Thomas Seyfried
SSEA-1 Is an Enrichment Marker for Tumor-Initiating Cells in Human Glioblastoma
Author links open overlay panelMyung JinSon1KevinWoolard1Do-HyunNam2JeongwuLee1Howard A.Fine1Show morehttps://doi.org/10.1016/j.stem.2009.03.003Get rights and contentUnder an Elsevier user licenseopen archive
CD133+ populations of human glioblastoma multiforme (GBM) cells are reportedly enriched for tumor stem cells (TSCs) or tumor-initiating cells (TICs). Approximately 40% of freshly isolated GBM specimens, however, do not contain CD133+ tumor cells, raising the possibility that CD133 may not be a universal enrichment marker for GBM TSCs/TICs. Here we demonstrate that stage-specific embryonic antigen 1(SSEA-1/LeX)+ GBM cells fulfill the functional criteria for TSC/TIC, since (1) SSEA-1+ cells are highly tumorigenic in vivo, unlike SSEA-1- cells; (2) SSEA-1+ cells can give rise to both SSEA-1+ and SSEA-1− cells, thereby establishing a cellular hierarchy; and (3) SSEA-1+ cells have self-renewal and multilineage differentiation potentials. A distinct subpopulation of SSEA-1+ cells was present in all but one of the primary GBMs examined (n = 24), and most CD133+ tumor cells were also SSEA-1+, suggesting that SSEA-1 may be a general TSC/TIC enrichment marker in human GBMs.
The cancer stem cell hypothesis posits that tumorigenic potential is largely restricted to a subset of self-renewing tumor cells with stem cell-like properties designated as tumor stem cells (TSCs) or tumor-initiating cells (TICs) (Clarke et al., 2006, Jordan et al., 2006, Reya et al., 2001). Since these TSCs/TICs represent only a subpopulation within the whole of the tumor, there is great interest in finding cell-surface markers that will allow the prospective identification and isolation of these cells (Uchida et al., 2000, Vescovi et al., 2006). The AC133 (later designated as CD133/PROM1) antigen was originally identified as a surface antigen expressed in hematopoietic stem cell populations (Corbeil et al., 1998, Miraglia et al., 1997). Weissman and colleagues have shown that human fetal brain cells expressing AC133 antigen have neural stem cell (NSC)-like properties (Uchida et al., 2000). Several groups have demonstrated that cell sorting for CD133 expression can enrich for TSC/TIC populations in brain tumors (Bao et al., 2006, Galli et al., 2004, Piccirillo et al., 2006, Singh et al., 2004) as well as in colon cancer (O’Brien et al., 2007, Ricci-Vitiani et al., 2007) and prostate cancer (Richardson et al., 2004). These CD133+ cells appear to be responsible for tumor initiation in vivo and are relatively resistant to radiation compared to the remaining bulk of tumor cells, suggesting their potential role in tumor recurrence (Bao et al., 2006).
…Similar to hematopoietic stem cells, probably the most thoroughly characterized stem cell population, a combination of markers will ultimately best define glioma TSCs/TICs (Dick, 2008, Kim et al., 2006, Weissman et al., 2001). Given the complex genetic and epigenetic heterogeneity of GBMs, it is unlikely that the expression of a single marker such as CD133 or SSEA-1 will define TICs in all tumors. Furthermore, if tumors originate from stem/progenitor cells at different points along the normal developmental pathway, TSCs/TICs from different subsets of gliomas may have different immunophenotypes and characteristic stem cell markers. Whether SSEA-1+ tumors represent a specific subtype of glioblastomas compared to CD133+ tumors is impossible to determine conclusively at this point due to the relatively small numbers of the established cell lines evaluated to date. Additionally, whether CD133 and/or SSEA-1 have functional properties in TSCs/TICs is an important question worthy of further study.
In conclusion, SSEA-1 appears to be an enrichment marker for glioblastoma-derived TSCs/TICs from CD133− tumors. Whether SSEA-1+ glioblastomas represent a distinct subset of glioblastomas compared to CD133+ tumors and whether there are additional markers that will further refine the identification of the specific TSC/TIC remain to be seen. Finally, it will be interesting to see whether SSEA-1 might represent a TSC/TIC marker for malignancies other than brain tumors.