Stem Cells, Cell Differentiation, and Cancer
Summary of Key Points
• Many tumors originate in organs and tissues that undergo a continuous process of cell turnover, which is sustained by a minority population of stem cells (e.g., the colon, breast, lung, prostate, brain, and bone marrow).
• Stem cells have four fundamental properties: the ability to give rise to new stem cells with intact and unlimited growth potential (self-renewal), the ability to give rise to a progeny of specialized cells (differentiation), the ability to migrate into new tissue locations and establish tissue growth (migration and tissue repair), and the ability to balance the previous three properties according to a genetic program that places constraints on their numerical expansion (homeostatic control).
• In many tissues, stem cells are the only long-lived cells. This observation suggests that early transforming events, either genetic mutations or epigenetic modifications, are likely to accumulate in stem cells.
• In addition to oncogenes that control cell survival and proliferation, there is a class of oncogenes that regulate self-renewal. In some cancers, tumor growth might be sustained by progenitor cells, which do not naturally self-renew but have aberrantly acquired this ability during disease progression.
• Experimental data suggest that, in many leukemias and solid tumors (e.g., breast, colon, head and neck, pancreas, bladder, and prostate carcinomas), only a specific, phenotypically distinct subset of cancer cells is able to form tumors when transplanted in mice.
• Currently, most antitumor drugs are evaluated on the basis of their capacity to rapidly reduce tumor size. However, because self-renewing cancer cells are often minority populations, treatments that simply reduce tumor size may not effectively target these cells.
• To result in cure, therapies must eradicate self-renewing cancer cells. The ability to identify these cells should allow the identification of new diagnostic markers and therapeutic targets.
A The capacity of selected cells to naturally undergo a process of full epigenetic reprogramming, which causes loss of differentiation identity and reversal to a totipotent stem cell state
B A fundamental property of stem cells that consists of the capacity to divide and give rise to functionally identical stem cells, with intact long-term expansion, proliferation, and differentiation potential
C The capacity possessed by stem cells to induce, when damaged, the dedifferentiation of neighboring daughter cells, thus creating new stem cells and renewing the stem cell pool
D A unique property possessed by mesenchymal stem cells, defined by the capacity to actively migrate out of a specific tissue and relocate into a new one, where they can change their epigenetic identity and acquire the function of other types of resident stem cells
2. What is the definition of “cancer stem cells?”
A Normal hematopoietic stem cells that migrated inside the tumor mass as the result of the strong inflammatory processes usually observed in cancer
