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Polyploid Giant Cancer Cells are dependent on cholesterol for progeny formation through amitotic division

ABSTRACT: Polyploid Giant Cancer Cells (PGCC) are increasingly being studied for their role in cancer recurrence and mortality. These cells are induced in bulk cancer cell populations when under stress such as hypoxia or treatment stress (i.e. chemotherapy or radiation). PGCC utilize temporary senescence achieved via a dedifferentiation pathway to survive transient stresses, providing a seed population for later regrowth. Our previous work demonstrated a dependence on the lysosomal enzyme acid ceramidase (ASAH1) in these cells, such that they are unable to perform division without ASAH1. The pro-drug LCL521 is lysosomally targeted, fully inhibits ASAH1 activity within 5 hours, and ablates the ability of PGCC to generate progeny while permitting mitotic cancer cells to proliferate normally. We used an RNASeq approach to compare the responses of parental PPC1 prostate cancer cells and their radiation-induced PGCC counterparts to 5 hours of LCL-521 treatment. RNASeq confirmed that no major changes were triggered in parental PPC1 cells while PGCC appeared to respond as if they had undergone cholesterol depletion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195919 | GEO | 2022/06/01

REPOSITORIES: GEO

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PGCC development and recovery within a prostate cancer cell population

Project description:Polyploid Giant Cancer Cells (PGCC) are increasingly being studied for their role in cancer recurrence and mortality. PGCC arise from cancer cells in response to stress such as radiation, chemotherapy, or hypoxia. PGCC remain viable but do not divide by mitosis. However, upon cessation of stress, PGCC are capable of progeny formation via primitive, amitotic mechanisms akin to budding or bursting. In this study, the initial PGCC offspring are referred to as “early progeny”. As early progeny cells resume proliferation they generate “late progeny”. This study assessed the transcriptional changes that occur as parental cancer cells progress to PGCC in response to radiation stress, escape as early progeny, and resume proliferation.

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Single-Cell Morphological and Transcriptome Analysis Unveil Inhibitors of Polyploid Giant Breast Cancer Cells In Vitro

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Project description:To understand the role of polyploid giant cancer cells (PGCCs) in drug resistance and disease relapse, we examined the mRNA expression profile of PGCCs in ovarian cancer cells. An acute activation of IL-6 dominated senescence associated secretory phenotype lasted 2-3 weeks and declined during the termination phase of polyploidy. IL-6 activates embryonic stemness during the initiation of PGCCs and can reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) via increased collagen synthesis, activation of VEGF expression, and enrichment of CAFs and the GPR77+/CD10+ fibroblast subpopulation. Blocking the IL-6 feedback loop with tocilizumab or apigenin prevented PGCC formation, attenuated embryonic stemness and the CAF phenotype, and inhibited tumor growth in a patient-derived xenograft high-grade serous ovarian carcinoma model. Thus, IL-6 derived by PGCCs is capable of reprogramming both cancer and stromal cells and contributes to the evolution and remodeling of cancer. Targeting IL-6 in PGCCs may represent a novel approach to combating drug resistance

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Project description:cDNA microarray study of X-radiation (XR) sensitive HCT116-CloneK cells 24 hours after XR treatment at 4Gy versus unirradiated HCT116-Clone10 cells. HCT116-Clone10 cells have similar XR response with parental HCT116 cells. Keywords = X-radiation (XR), XR sensitive, colorectal cancer cells, HCT1116 Keywords: repeat sample

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2003-12-08 | GSE525 | GEO

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