A hypothetical anti-neoplastic mechanism associated to reserve cells.
Reserve-stem cells, the permanent cells of body tissues, are thought to be the progenitor cells of cancer. This concept originates from the assumption that accumulation of somatic mutations necessary for malignant transformation can only take place in cellular targets with a prolonged life span. The progeny of reserve cells entering the differentiative pathway would be protected from potential critical mutations happening later than the reserve cell stage by normal cell population replacement unless possible targets would escape the replacement process by further mutations extending the cell's life span, impairment of physiological apoptosis. The existence of a mechanism for maintenance of genetic integrity in stem/reserve cells has previously been proposed. This mechanism differs from already identified DNA repair systems and, potentially, could prevent malignant transformation at the reserve cell stage, counteracting the expected high propensity of stem/reserve cells to neoplastic proliferation. Here, we show some histopathological observations suggesting that an anti-cancer mechanism might be associated to reserve/stem cells and that it could be responsible for huge differences in cancer incidence between closely related body sites. Furthermore, primary impairment of this protective mechanism might characterize the oncogenic pathway responsible for tumors of primitive cells. Several features of the histopathological observations presented lead us to propose that the underlying molecular mechanism may involve the telomere complex.
Torres-Montaner
Antonio
A
Departamento de Anatomía Patológica, Hospital Universitario de Puerto Real, C/Nacional IV, km 665, Puerto Real, Cádiz 11510, Spain. a.torres.m@comcadiz.com
Hughes
David
D
D000818:Animals; D002455:Cell Division; D004260:DNA Repair; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*; D016615:Telomere