Research Progress on the Mechanism of Tumor Resistance in Polyploid Giant Cancer Cells

doi:10.12280/gjfckx.20240393

Abstract

Abstract:

Chemotherapy is a commonly used method for tumor treatment, which has a positive effect in the early stage of tumor treatment. However, as the chemotherapy course increases, the sensitivity of tumor cells to chemotherapy drugs gradually weakens, leading to chemotherapy resistance. Tumor drug resistance is a complex process mediated by multiple factors, which is currently believed to be related to tumor cell stemness, heterogeneity, tumor immune microenvironment, and increased chemotherapy drug transport and efflux. But the specific mechanism is not yet clear. Polyploid giant cancer cells(PGCCs) are a special subset of tumor cells with increased volume and abundant nuclei. Research has found that PGCC generally exist in colorectal cancer, breast cancer, ovarian cancer and other tumors, and were closely related to the occurrence, metastasis, drug resistance and recurrence of tumors. This paper describes the formation and significance of the research progress of PGCC in tumors, and expounds the possible mechanism of PGCC causing drug resistance from the perspective of its special mechanism, autophagy, aging and DNA repair, so as to provide a possible strategy for improving tumor drug resistance.

Key words: Neoplasms, Polyploid giant cancer cells, Drug resistance, neoplasm, Autophagy, DNA repair

DING Yi-ling, LU Di, SONG Dian-rong. Research Progress on the Mechanism of Tumor Resistance in Polyploid Giant Cancer Cells[J]. Journal of International Obstetrics and Gynecology, 2024, 51(4): 361-365.

References 37

[1]	Li X, Zhong Y, Zhang X, et al. Spatiotemporal view of malignant histogenesis and macroevolution via formation of polyploid giant cancer cells[J]. Oncogene, 2023, 42(9):665-678. doi: 10.1038/s41388-022-02588-0. pmid: 36596845
[2]	Zhou X, Zhou M, Zheng M, et al. Polyploid giant cancer cells and cancer progression[J]. Front Cell Dev Biol, 2022,10:1017588. doi: 10.3389/fcell.2022.1017588.
[3]	Forkner CE. The origin and fate of two types of multi-nucleated giant cells in the circulating blood[J]. J Exp Med, 1930, 52(2):279-297. doi: 10.1084/jem.52.2.279. pmid: 19869765
[4]	Heppner GH. Tumor heterogeneity[J]. Cancer Res, 1984, 44(6):2259-2265. pmid: 6372991
[5]	Solari F, Domenget C, Gire V, et al. Multinucleated cells can continuously generate mononucleated cells in the absence of mitosis: a study of cells of the avian osteoclast lineage[J]. J Cell Sci, 1995, 108(Pt 10):3233-3241. doi: 10.1242/jcs.108.10.3233.
[6]	Erenpreisa JA, Cragg MS, Fringes B, et al. Release of mitotic descendants by giant cells from irradiated Burkitt's lymphoma cell line[J]. Cell Biol Int, 2000, 24(9):635-648. doi: 10.1006/cbir.2000.0558. pmid: 10964453
[7]	Erenpreisa J, Kalejs M, Ianzini F, et al. Segregation of genomes in polyploid tumour cells following mitotic catastrophe[J]. Cell Biol Int, 2005, 29(12):1005-1011. doi: 10.1016/j.cellbi.2005.10.008. pmid: 16314119
[8]	Niu N, Zhang J, Zhang N, et al. Linking genomic reorganization to tumor initiation via the giant cell cycle[J]. Oncogenesis, 2016, 5(12):e281. doi: 10.1038/oncsis.2016.75.
[9]	Zhang S, Mercado-Uribe I, Xing Z, et al. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells[J]. Oncogene, 2014, 33(1):116-128. doi: 10.1038/onc.2013.96. pmid: 23524583
[10]	You B, Xia T, Gu M, et al. AMPK-mTOR-Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells[J]. Cancer Res, 2022, 82(5):846-858. doi: 10.1158/0008-5472.CAN-21-2342.
[11]	Zhang Z, Feng X, Deng Z, et al. Irradiation-induced polyploid giant cancer cells are involved in tumor cell repopulation via neosis[J]. Mol Oncol, 2021, 15(8):2219-2234. doi: 10.1002/1878-0261.12913. pmid: 33523579
[12]	Lopez-Sánchez LM, Jimenez C, Valverde A, et al. CoCl₂, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer[J]. PLoS One, 2014, 9(6):e99143. doi: 10.1371/journal.pone.0099143.
[13]	Mannan R, Wang X, Bawa PS, et al. Polypoidal giant cancer cells in metastatic castration-resistant prostate cancer: observations from the Michigan Legacy Tissue Program[J]. Med Oncol, 2020, 37(3):16. doi: 10.1007/s12032-020-1341-6. pmid: 32030484
[14]	Fei F, Qu J, Liu K, et al. The subcellular location of cyclin B1 and CDC25 associated with the formation of polyploid giant cancer cells and their clinicopathological significance[J]. Lab Invest, 2019, 99(4):483-498. doi: 10.1038/s41374-018-0157-x. pmid: 30487595
[15]	Adibi R, Moein S, Gheisari Y. Cisplatin-Resistant Ovarian Cancer Cells Reveal a Polyploid Phenotype with Remarkable Activation of Nuclear Processes[J]. Adv Biomed Res, 2023,12:77. doi: 10.4103/abr.abr_348_21.
[16]	Zhang L, Wu C, Hoffman RM. Prostate Cancer Heterogeneous High-Metastatic Multi-Organ-Colonizing Chemo-Resistant Variants Selected by Serial Metastatic Passage in Nude Mice Are Highly Enriched for Multinucleate Giant Cells[J]. PLoS One, 2015, 10(11):e0140721. doi: 10.1371/journal.pone.0140721.
[17]	Li Z, Zheng M, Zhang H, et al. Arsenic Trioxide Promotes Tumor Progression by Inducing the Formation of PGCCs and Embryonic Hemoglobin in Colon Cancer Cells[J]. Front Oncol, 2021,11:720814. doi: 10.3389/fonc.2021.720814.
[18]	Tagal V, Roth MG. Loss of Aurora Kinase Signaling Allows Lung Cancer Cells to Adopt Endoreplication and Form Polyploid Giant Cancer Cells That Resist Antimitotic Drugs[J]. Cancer Res, 2021, 81(2):400-413. doi: 10.1158/0008-5472.CAN-20-1693. pmid: 33172929
[19]	Jiao Y, Yu Y, Zheng M, et al. Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis[J]. Clin Transl Med, 2024, 14(2):e1567. doi: 10.1002/ctm2.1567. pmid: 38362620
[20]	徐磊, 武寒, 王苗苗, 等. 干预自噬调控p62-Keap1/Nrf2-GPX4通路对结直肠癌细胞铁死亡及奥沙利铂耐药的影响[J]. 临床与实验病理学杂志, 2024, 40(2):133-144. doi: 10.13315/j.cnki.cjcep.2024.02.006.
[21]	陶克龙, 张振兴, 徐关根, 等. hsa-circ-002179靶向miR-143-3p调控自噬-凋亡平衡在胃癌5-氟尿嘧啶化疗耐药性中的作用研究[J]. 浙江中西医结合杂志, 2024, 34(1):21-27. doi: 10.3969/j.issn.1005-4561.2024.01.005.
[22]	Bojko A, Staniak K, Czarnecka-Herok J, et al. Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells[J]. Int J Mol Sci, 2020, 21(17):6084. doi: 10.3390/ijms21176084.
[23]	White-Gilbertson S, Lu P, Saatci O, et al. Transcriptome analysis of polyploid giant cancer cells and their progeny reveals a functional role for p21 in polyploidization and depolyploidization[J]. J Biol Chem, 2024, 300(4):107136. doi: 10.1016/j.jbc.2024.107136.
[24]	Zhang X, Yao J, Li X, et al. Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer[J]. Sci Adv, 2023, 9(29):eadf7195. doi: 10.1126/sciadv.adf7195.
[25]	Färkkilä A, Rodríguez A, Oikkonen J, et al. Heterogeneity and Clonal Evolution of Acquired PARP Inhibitor Resistance in TP53- and BRCA1-Deficient Cells[J]. Cancer Res, 2021, 81(10):2774-2787. doi: 10.1158/0008-5472.CAN-20-2912. pmid: 33514515
[26]	Zheng L, Dai H, Zhou M, et al. Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression[J]. Nat Commun, 2012,3:815. doi: 10.1038/ncomms1825.
[27]	Thura M, Ye Z, Al-Aidaroos AQ, et al. PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse[J]. Commun Biol, 2021, 4(1):923. doi: 10.1038/s42003-021-02449-8. pmid: 34326464
[28]	Chen BW, Zhou Y, Wei T, et al. lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p[J]. J Cell Biochem, 2021, 122(1):130-142. doi: 10.1002/jcb.29844.
[29]	刘晓冬, 武晓萌, 王冬, 等. GP73通过EMT调节肝癌细胞对奥沙利铂耐药[J]. 药物评价研究, 2021, 44(5):1004-1009. doi: 10.7501/j.issn.1674-6376.2021.05.014.
[30]	Fan L, Zheng M, Zhou X, et al. Molecular mechanism of vimentin nuclear localization associated with the migration and invasion of daughter cells derived from polyploid giant cancer cells[J]. J Transl Med, 2023, 21(1):719. doi: 10.1186/s12967-023-04585-7. pmid: 37833712
[31]	Xuan B, Ghosh D, Jiang J, et al. Vimentin filaments drive migratory persistence in polyploidal cancer cells[J]. Proc Natl Acad Sci U S A, 2020, 117(43):26756-26765. doi: 10.1073/pnas.2011912117.
[32]	Thongchot S, Vidoni C, Ferraresi A, et al. Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse[J]. Cancers (Basel), 2021, 13(9):2134. doi: 10.3390/cancers13092134.
[33]	Zhou L, Li J, Liao M, et al. LncRNA MIR155HG induces M2 macrophage polarization and drug resistance of colorectal cancer cells by regulating ANXA2[J]. Cancer Immunol Immunother, 2022, 71(5):1075-1091. doi: 10.1007/s00262-021-03055-7.
[34]	Min A, Mimura K, Nakajima S, et al. Therapeutic potential of anti-VEGF receptor 2 therapy targeting for M2-tumor-associated macrophages in colorectal cancer[J]. Cancer Immunol Immunother, 2021, 70(2):289-298. doi: 10.1007/s00262-020-02676-8.
[35]	Parekh A, Das S, Parida S, et al. Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo[J]. Oncogene, 2018, 37(33):4546-4561. doi: 10.1038/s41388-018-0272-6. pmid: 29743594
[36]	Liu Y, Shi Y, Wu M, et al. Hypoxia-induced polypoid giant cancer cells in glioma promote the transformation of tumor-associated macrophages to a tumor-supportive phenotype[J]. CNS Neurosci Ther, 2022, 28(9):1326-1338. doi: 10.1111/cns.13892.
[37]	Niu N, Yao J, Bast RC, et al. IL-6 promotes drug resistance through formation of polyploid giant cancer cells and stromal fibroblast reprogramming[J]. Oncogenesis, 2021, 10(9):65. doi: 10.1038/s41389-021-00349-4. pmid: 34588424