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Turkish Journal of Biology

Abstract

Background/aim: Polyploid giant cancer cells (PGCCs) have been implicated in tumor recurrence, therapeutic resistance, and cellular plasticity; however, the biological properties of PGCC-derived daughter cells (PGCC-DCs) in gastric cancer remain poorly understood. The present study aimed to evaluate the molecular and functional characteristics of these progeny cells in a gastric cancer model.

Methods: The PGCCs were induced in HGC-27 gastric cancer cells using cobalt(II) chlorideCoCl2-mediated hypoxic stress and enriched by size-based filtration. The PGCC-DCs were isolated through single-cell culture and characterized using molecular and functional assays. Clinical assessments of the cellular parameters were conducted by comparing the PGCC-DCs with parental cells.

Results: Compared with the parental cells, the PGCC-DCs showed increased expression of stemness-, epithelial–mesenchymal transition-, hypoxia-, and survival-associated genes. The PGCC-DCs also displayed elevated CD44, hypoxia-inducible factor 1-alpha (HIF-1α), interleukin-6 (IL-6), and p21 protein levels; enhanced invasion and spheroid formation; and marked resistance to 5-fluorouracil (5- FU). Additionally, the PGCC-DCs also displayed reduced levels of intracellular reactive oxygen species and mitochondrial membrane potential. Pharmacological treatment with the HIF-1α inhibitor YC-1 attenuated stemness-associated features, suppressed aggressive phenotypes, and increased sensitivity to 5-FU.

Conclusion: These results suggest that PGCC-DCs exhibit an aggressive, chemoresistant phenotype in the HGC-27 model, and that HIF-1α-associated signaling may contribute to these characteristics.

Author ORCID Identifier

ÖZLEM TÜRKSOY TERZİOĞLU: 0000-0002-0497-4991

DOI

10.55730/1300-0152.2986

Keywords

Polyploid giant cancer cells, gastric cancer, daughter cells, hypoxia signaling, stemness, chemoresistance

First Page

437

Last Page

451

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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Biology Commons

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