Intratumoral heterogeneity model and cancer stem cells in human ovarian cancer

  • Heterogeneous populations may contain subpopulations with different phenotypic and genetic profiles. Among these are cancer stem cell-like cells (CSCs), a dynamically changing subpopulation of cancer-initiating cells (CICs) that arises due to the acquisition of malignant cellular transformations as part of a biological evolutionary process. Although, in theory, many tumors contain limited minority of CSCs, in practice, it is difficult to identify the cells that acquire the genetic/epigenetic alterations that lead to tumor initiation. As the name suggests, the CSC hypothesis describes a process driven by rare cellular components that display stem cell properties of self-renewal and differentiation: self-renewal promotes tumorigenesis, whereas differentiation contributes to the phenotypic heterogeneity of tumors.
  • The role of CSCs as adverse factors in ovarian cancer may reflect their suggested origin from aberrant CICs. Consistent with this, a subpopulation of cells isolated from mouse ovarian cancer cell lines and ascites of human ovarian cancer patients phenotypically resemble stem cells. CSCs are thought to be self-renewing and possess multipotency. This latter property enables CSCs to differentiate into diverse cells that display histologic heterogeneity and tumorigenicity, even in a subpopulation or a small minority of cells.

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