Stress-Induced Polyploid Giant Cancer Cells: Unique Way of Formation and Non-Negligible Characteristics

Abstract

Polyploidy is a conserved mechanism in cell development and stress responses. Multiple stresses of treatment, including radiation and chemotherapy drugs, can induce the polyploidization of tumor cells. Through endoreplication or cell fusion, diploid tumor cells convert into giant tumor cells with single large nuclei or multiple small nucleuses. Some of the stress-induced colossal cells, which were previously thought to be senescent and have no ability to proliferate, can escape the fate of death by a special way. They can remain alive at least before producing progeny cells through asymmetric cell division, a depolyploidization way named neosis. Those large and danger cells are recognized as polyploid giant cancer cells (PGCCs). Such cells are under suspicion of being highly related to tumor recurrence and metastasis after treatment and can bring new targets for cancer therapy. However, differences in formation mechanisms between PGCCs and well-accepted polyploid cancer cells are largely unknown. In this review, the methods used in different studies to induce polyploid cells are summarized, and several mechanisms of polyploidization are demonstrated. Besides, we discuss some characteristics related to the poor prognosis caused by PGCCs in order to provide readers with a more comprehensive understanding of these huge cells.

Oncogenic RABL6A promotes NF1-associated MPNST progression in vivo

“…Atypia and polyploidy (seen as enlarged cells with aberrant nuclei) are morphological features of malignancy resulting from stress and accumulated genomic instability. 36 , 37 We previously showed that silencing Rabl6 in cultured mouse embryo fibroblasts induces genomic instability in the form of centrosome amplification and multinucleation. 24 Using mouse MPNST cell lines derived from wild-type mice with NC or NP tumors, we evaluated the effects of acute Rabl6 knockdown on both of those aberrant events ( Supplementary Figure 3A ).…”

“… 24 Using mouse MPNST cell lines derived from wild-type mice with NC or NP tumors, we evaluated the effects of acute Rabl6 knockdown on both of those aberrant events ( Supplementary Figure 3A ). Downregulation of endogenous RABL6A caused significant increases in enlarged, multinucleated cells ( Supplementary Figure 3B ) akin to polyploid giant cancer cells 36 as well as centrosome amplification ( Supplementary Figure 3C ) in both NC and NP-derived MPNST cell lines. Basal levels of centrosome amplification trended higher in cultured NP cells compared to NC cells although differences were not statistically significant ( Supplementary Figure 3C ).…”

“…Notably, the presence of enlarged polyploid cells (also called “polyploid giant cancer cells”), which was most prevalent in NP tumors lacking RABL6A and similarly seen after acute RABL6A silencing in cultured NC and NP cells, has been associated with higher risk of tumor recurrence and metastasis. 36 …”

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Hence, efforts have been made on searching for alternatives to generate polyploid cancer cells at laboratory scale. [14][15][16][17] In particular, the type known as Polyploid (which was not certified by peer review) is the author/funder. All rights reserved.…”

“…42°C) have been also reported as traditional strategy to stimulate their rising. [14][15][16][17] However, it is important to note that none of these stimuli properly resemble the conditions sensed by cancer cells located inside primary tumors. Thus, with the purpose to stimulate the formation of polynucleated cells in milieus resembling the biophysical properties already described for malignant tissues, other strategies have been tested.…”