CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS

Authors

  • D. Endoh Graduate School of Food and Nutritional Sciences, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • K. Ishii Graduate School of Food and Nutritional Sciences, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • K. Kohno Research Institute of Life Innovation, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • N. Virgona Research Institute of Life Innovation, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • Y. Miyakoshi Research Institute of Life Innovation, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • T. Yano Research Institute of Life Innovation, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan
  • T. Ishida Research Institute of Life Innovation, Toyo University, 1-1-1 Izumino, Oura-gun, Gunma 374-0193, Japan

DOI:

https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.18045

Keywords:

chemoresistance, hypoxia, mesothelioma, stemness, tumor spheroid

Abstract

Background: Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids. Materials and Methods: Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels. Results: Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia. Conclusion: From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

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Published

26.05.2023

How to Cite

Endoh, D., Ishii, K., Kohno, K., Virgona, N., Miyakoshi, Y., Yano, T., & Ishida, T. (2023). CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS. Experimental Oncology, 44(2), 121–125. https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.18045

Issue

Vol. 44 No. 2 (2022): Experimental Oncology

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Original contributions

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