Entosis: From Cell Biology to Clinical Cancer Pathology

Simple Summary We review published clinico-histopathological studies establishing entosis an important prognostic and predictor factor in various cancer types. We also propose a new model to study this phenomenon, which involves active entry of one cell into another one. The internalized cell can remain viable and leave the host cell after a long time, potentially leading to cancer recurrence. Entotic figures are cell in cell structures, in which the nucleus of external cell is crescent-shaped, and the inner cell is surrounded by the extensive space entotic vacuole, distinguishing entosis from cell cannibalism. Entosis correlates with cancer worse prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma, and some breast ductal carcinoma. The BxPC-3 pancreatic cancer cells provide a new, more convenient model for entosis research in comparison to the previously described semidherent MCF7 model. BxPC-3 cells undergo and survive spontaneous entosis in normal adherent culture conditions. Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.