Publication Date
8-3-2021
Journal
Biology of Reproduction
DOI
10.1093/biolre/ioab102
PMID
34037700
PMCID
PMC8335353
PubMedCentral® Posted Date
5-25-2021
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Animals, Female, Giant Cells, Humans, Mice, Mitosis, Ovarian Neoplasms, Polyploidy, ovarian cancer, cytotoxic stress, mitosis, polyploidy, endoreplication, polyploid giant cancer cells, p53
Abstract
Current first-line treatment of patients with high-grade serous ovarian cancer (HGSOC) involves the use of cytotoxic drugs that frequently lead to recurrent tumors exhibiting increased resistance to the drugs and poor patient survival. Strong evidence is accumulating to show that HGSOC tumors and cell lines contain a subset of cells called polyploidy giant cancer cells (PGCCs) that act as stem-like, self-renewing cells. These PGCCs appear to play a key role in tumor progression by generating drug-resistant progeny produced, in part, as a consequence of utilizing a modified form of mitosis known as endoreplication. Thus, developing drugs to target PGCCs and endoreplication may be an important approach for reducing the appearance of drug-resistant progeny. In the review, we discuss newly identified regulatory factors that impact mitosis and which may be altered or repurposed during endoreplication in PGCCs. We also review recent papers showing that a single PGCC can give rise to tumors in vivo and spheroids in culture. To illustrate some of the specific features of PGCCs and factors that may impact their function and endoreplication compared to mitosis, we have included immunofluorescent images co-localizing p53 and specific mitotic regulatory, phosphoproteins in xenografts derived from commonly used HGSOC cell lines.
Included in
Diseases Commons, Medical Sciences Commons, Obstetrics and Gynecology Commons, Oncology Commons, Women's Health Commons
Comments
Associated Data