Abstract
Simple SummaryWe 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.
Highlights
Entosis refers to the invasion of one living cell into another of the same type with involvement of adhesion molecules, actin cytoskeleton and expenditure of energy [1,2]
Entosis is frequently found during histopathological examination of specimens obtained from various human cancers
Cancer tissues with numerous entotic figures usually represent a more malignant phenotype, which could result from the beneficial effects of entosis for malignant cells
Summary
Entosis refers to the invasion of one living cell into another of the same type with involvement of adhesion molecules, actin cytoskeleton and expenditure of energy [1,2]. Entotic cells can be eliminated through regulated cell death within the entotic vacuole (entosome), via a specific autophagy-related process, commonly known as LC3-associated phagocytosis (LAP) [4]. This process is independent of the apoptotic pathway [2]. After cell invasion into the host cell, the inner cell is surrounded by a double membrane of the entotic vacuole, with an extensive space between membranes. The presence of the entotic vacuole is a feature distinguishing entosis from cell cannibalism, in which the phagocytosed cell is surrounded by a thin double-membrane space, with subsequent digestion of the inner membrane [2]. We highlight the potential relationship of cell adhesion with the fate of entotic cells in vitro, based on the model of BxPc3 cells
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