Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

摘要: Until recently, acquired resistance to cytostatics had mostly been attributed biochemical mechanisms such as decreased intake and/or increased efflux of therapeutics, enhanced DNA repair, and altered activity or deregulation target proteins. Although these have widely investigated, little is known about membrane barriers responsible for the chemical imperviousness cell compartments cellular segregation in cytostatic-treated tumors. In highly heterogeneous cross-resistant radiorefractory populations selected by exposure anticancer agents, we found a number atypical recurrent types (1) tumor cultures different embryonic origins, (2) mouse xenografts, (3) paraffin sections from patient Alongside morphologic peculiarities, presented cancer stem markers, aberrant signaling pathways, set deregulated miRNAs confer both stem-cell phenotypes aggressive behavior. The first type, named spiral cells, marked arrangement nuclei. second monastery characterized prominent walls inside which daughter cells can be seen maturing amid rich mitochondrial environment. third called pregnant giant with syncytium-like morphology, main nucleus, many endoreplicative functional progeny cells. A rare fourth type identified leukemia was christened shepherd it always associated clusters smaller Furthermore, portion resistant displayed nuclear encapsulation via aggregation perimeter response cytostatic insults, probably conferring drugs long periods dormancy until eclosion takes place. This phenomenon correlated an increase intracellular intercellular traffic well uptake free extracellular mitochondria. All disorders could, fact, untreated but were more pronounced entities, suggesting natural mechanism survival triggered injury, primitive strategy ensure stemming, self-renewal, differentiation under adverse conditions, fact that may play significant role chemotherapy outcomes.