The effects of anticancer treatments on cell heterogeneity and their proliferative potential play an important role in tumor persistence and metastasis. However, little is known about de-polyploidization, cell fate, and physiological stemness of the resulting cell populations. Here we describe a distinctive cell type termed "pregnant" P1 cells found within chemotherapy refractory ovarian tumors, which generate and gestate daughter generation Gn-cells intracytoplasmically. Release of Gn-cells occurred by ejection through crevices in P1 cell membrane by body contractions or using a funiculus-like structure. These events characterized a not yet described mechanism of cell segregation. Maternal P1-cells were principally capable of surviving parturition events and continued to breed and nurture Gn progenies. In addition, P1-cells were competent to horizontally transmit offspring Gn-cells into other specific proximal cells, injecting them to receptor R1-cells via cell-cell tunneling. This process represents a new mechanism used by tumor cells to invade surrounding tissues and ensure life cycles. In contrast to the pregnant P1-cells with low expression of stem cell markers despite their physiological stemness, the first offspring generations of daughter G1-cells expressed high levels of ovarian cancer stem cell markers. Furthermore, both P1- and Gn-cells overexpressed multiple human endogenous retroviral envelope proteins. Moreover, programmed death-ligand 1 and the immunosuppressive domain of the retroviral envelope proteins were also overexpressed in P1-cells, suggesting effective protection against the host immune system. Together, our data suggest that P1 oncogenerative cancer cells exhibit a not yet described cell-biological mechanism of persistence and transmission of malignant cells in patients with advanced cancers.
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Δευτέρα 12 Φεβρουαρίου 2018
A distinct oncogenerative multinucleated cancer cell serves as a source of stemness and tumor heterogeneity
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