Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis

Jiao, Yuqi; Yu, Yongjun; Zheng, Minying; Yan, Man; Wang, Jiangping; Zhang, Yue; Zhang, Shiwu

doi:10.1002/ctm2.1567

Cited by 8 publications

(1 citation statement)

References 204 publications

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“…PGCCs play a detrimental role in cancer dormancy and reactivation, leading to disease recurrence. PGCCs enter dormancy through aberrant cell cycles mediated by P53 and CDK inhibitors and can exit dormancy by producing daughter cells ( Jiao et al, 2024 ). A recent study by Zheng et al found that after CoCl 2 treatment, the expression of Cdc42 and PAK1 increased, promoting the nuclear expression of phosphorylated stathmin (STMN1).…”

Section: Therapies Targeting Pgccsmentioning

confidence: 99%

Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation

Liu,

Wang,

2024

Front. Cell Dev. Biol.

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Polyploid giant cancer cells (PGCCs) are characterized by the presence of either a single enlarged nucleus or multiple nuclei and are closely associated with tumor progression and treatment resistance. These cells contribute significantly to cellular heterogeneity and can arise from various stressors, including radiation, chemotherapy, hypoxia, and environmental factors. The formation of PGCCs can occur through mechanisms such as endoreplication, cell fusion, cytokinesis failure, mitotic slippage, or cell cannibalism. Notably, PGCCs exhibit traits similar to cancer stem cells (CSCs) and generate highly invasive progeny through asymmetric division. The presence of PGCCs and their progeny is pivotal in conferring resistance to chemotherapy and radiation, as well as facilitating tumor recurrence and metastasis. This review provides a comprehensive analysis of the origins, potential formation mechanisms, stressors, unique characteristics, and regulatory pathways of PGCCs, alongside therapeutic strategies targeting these cells. The objective is to enhance the understanding of PGCC initiation and progression, offering novel insights into tumor biology.

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Section: Therapies Targeting Pgccsmentioning

confidence: 99%

Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation

Liu,

Wang,

2024

Front. Cell Dev. Biol.

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Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion

Hirose,

Osaki,

Kamm

2024

Preprint

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Metastasis, the leading cause of cancer-related deaths, involves a complex cascade of events, including extravasation. Despite extensive research into metastasis, the mechanisms underlying extravasation remain unclear. Molecular targeted therapies have advanced cancer treatment, yet their efficacy is limited, prompting exploration into novel therapeutic targets. Here, we showed the association of polyploidy in MDA-MB-231 breast cancer cells and their extravasation, using microfluidic systems to reproduce the in vivo microvascular environment. We observed enhanced extravasation in polyploid cells alongside upregulated expression of genes involved in cell-substrate adhesion and cell mechanical dynamics. These findings offer insights into the relationship between polyploidy and extravasation, highlighting potential targets for cancer therapy.

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Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress

Pudełek,

Ryszawy,

Piwowarczyk

et al. 2024

J Transl Med

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Background Multi-drug resistance of poly(morpho)nuclear giant cells (PGCs) determines their cytoprotective and generative potential in cancer ecosystems. However, mechanisms underlying the involvement of PGCs in glioblastoma multiforme (GBM) adaptation to chemotherapeutic regimes remain largely obscure. In particular, metabolic reprogramming of PGCs has not yet been considered in terms of GBM recovery from doxorubicin (DOX)-induced stress. Methods Long-term proteomic and metabolic cell profiling was applied to trace the phenotypic dynamics of GBM populations subjected to pulse DOX treatment in vitro, with a particular focus on PGC formation and its metabolic background. The links between metabolic reprogramming, drug resistance and drug retention capacity of PGCs were assessed, along with their significance for GBM recovery from DOX-induced stress. Results Pulse DOX treatment triggered the transient formation of PGCs, followed by the appearance of small expanding cell (SEC) clusters. Development of PGCs was accompanied by the mobilization of their metabolic proteome, transient induction of oxidative phosphorylation (OXPHOS), and differential intracellular accumulation of NADH, NADPH, and ATP. The metabolic background of PGC formation was confirmed by the attenuation of GBM recovery from DOX-induced stress following the chemical inhibition of GSK-3β, OXPHOS, and the pentose phosphate pathway. Concurrently, the mobilization of reactive oxygen species (ROS) scavenging systems and fine-tuning of NADPH-dependent ROS production systems in PGCs was observed. These processes were accompanied by perinuclear mobilization of ABCB1 and ABCG2 transporters and DOX retention in the perinuclear PGC compartments. Conclusions These data demonstrate the cooperative pattern of GBM recovery from DOX-induced stress and the crucial role of metabolic reprogramming of PGCs in this process. Metabolic reprogramming enhances the efficiency of self-defense systems and increases the DOX retention capacity of PGCs, potentially reducing DOX bioavailability in the proximity of SECs. Consequently, the modulation of PGC metabolism is highlighted as a potential target for intervention in glioblastoma treatment.

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Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis

Cited by 8 publications

References 204 publications

Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation

Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation

Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion

Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress

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