Re-Evaluating Cancer Stem Cells (CSCs) and Polyploid Giant Cancer Cells (PGCCs) in the Light of Evolutionary Cancer Cell Biology ECCB

According to evolutionary cancer cell biology ECCB, cancer stem cells do not arise from normal stem cells, but rather from the functional ACD phenotype of the germline. This phenotype proliferates through asymmetric cell division, producing self-renewing cells and non-proliferating daughter cells with cancer stem cell qualities (CSCs). ECCB posits that cancer stem cells themselves do not proliferate. Similar to protists, there is a close reciprocal relationship between both sister cells that collectively form a germ and stem cell lineage. These sister cells share functional roles: the proliferating cancer germline cells generate stem cells, while the non-proliferating cancer stem cells accumulate progenitor cells for new germline clones. ECCB distinguishes between primary CSCs, which are associated with carcinogenesis and primary tumors, and secondary CSCs, which are linked to metastases. This unicellular stem cell system is homologous to that of parasitic protists, such as amoebae. Both cancer stem cells and amoebae stem cells are generated by an oxygen-sensitive germline and are vulnerable to damage when oxygen levels exceed 6.0% (germline hyperoxia). Oxygen concentrations above this threshold can damage the germline genome. Dysfunctional germline cells do not undergo senescence; instead, they continue to cycle through defective symmetric cell cycles However, to regain functionality, the germline genome requires repair by hyperpolyploid giant cells known as native PGCCs, which are homologous to the multinucleated genome repair structures MGRS found in protists. Native PGCCs differ in some respects from genotoxic-induced PGCCs