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Review

Entosis: From Cell Biology to Clinical Cancer Pathology

1
Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warszawa, Poland
2
Department of Pathology, West Pomeranian Hospital in Gryfice, 72-300 Gryfice, Poland
3
HESA Association at the Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warszawa, Poland
4
Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland
5
US Cardiovascular, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work and are first authors (I.M.-B. & I.D.).
Received: 26 June 2020 / Revised: 28 August 2020 / Accepted: 30 August 2020 / Published: 1 September 2020
(This article belongs to the Section Cancer Pathophysiology)
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. View Full-Text
Keywords: entosis; cancer; cell internalisation; cell-in-cell; cell adhesion; cancer prognosis; cancer predictor factor entosis; cancer; cell internalisation; cell-in-cell; cell adhesion; cancer prognosis; cancer predictor factor
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MDPI and ACS Style

Mlynarczuk-Bialy, I.; Dziuba, I.; Sarnecka, A.; Platos, E.; Kowalczyk, M.; Pels, K.K.; Wilczynski, G.M.; Wojcik, C.; Bialy, L.P. Entosis: From Cell Biology to Clinical Cancer Pathology. Cancers 2020, 12, 2481. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092481

AMA Style

Mlynarczuk-Bialy I, Dziuba I, Sarnecka A, Platos E, Kowalczyk M, Pels KK, Wilczynski GM, Wojcik C, Bialy LP. Entosis: From Cell Biology to Clinical Cancer Pathology. Cancers. 2020; 12(9):2481. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092481

Chicago/Turabian Style

Mlynarczuk-Bialy, Izabela, Ireneusz Dziuba, Agnieszka Sarnecka, Emilia Platos, Magdalena Kowalczyk, Katarzyna K. Pels, Grzegorz M. Wilczynski, Cezary Wojcik, and Lukasz P. Bialy 2020. "Entosis: From Cell Biology to Clinical Cancer Pathology" Cancers 12, no. 9: 2481. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12092481

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