Bladder cancer cell lines adapt their aggressiveness profile to oxygen tension

Oncol Lett. 2022 May 20;24(1):220. doi: 10.3892/ol.2022.13341. eCollection 2022 Jul.

Abstract

During the process of tumor growth, cancer cells will be subjected to intermittent hypoxia. This results from the delay in the development of the vascular network in relation to the proliferation of cancer cells. The hypoxic nature of a tumor has been demonstrated as a negative factor for patient survival. To evaluate the impact of hypoxia on the survival and migration properties of low and high-grade bladder cancer cell lines, two low-grade (MGHU-3 and SW-780) and two high-grade (SW-1710 and T24) bladder cancer cell lines were cultured in normoxic (20% O2) or hypoxic atmospheric conditions (2% O2). The response of bladder cancer cell lines to hypoxic atmospheric cell culture conditions was examined under several parameters, including epithelial-mesenchymal transition, doubling time and metabolic activities, thrombospondin-1 expression, whole Matrix Metallo-Proteinase activity, migration and resistance to oxidative stress. The low-grade cell line response to hypoxia was heterogeneous even if it tended to adopt a more aggressive profile. Hypoxia enhanced migration and pro-survival properties of MGHU-3 cells, whereas these features were reduced for the SW-780 cell line cultured under low oxygen tension. The responses of tested high-grade cell lines were more homogeneous and tended to adopt a less aggressive profile. Hypoxia drastically changed some of the bladder cancer cell line properties, for example matrix metalloproteinases expression for all cancer cells but also switch in glycolytic metabolism of low grade cancer cells. Overall, studying bladder cancer cells in hypoxic environments are relevant for the translation from in vitro findings to in vivo context.

Keywords: angiogenesis; cell death; extracellular matrix; hypoxia; migration; proliferation.

Grants and funding

This study was supported by grants from the Fonds de la Recherche en Santé du Québec (Quebec Health Research Fund), the Canadian Institutes of Health Research (grant no. #258229) and the CHU de Québec Foundation and the Canadian Urological Association Scholarship Fund. This study was in part funded by the Quebec Cell, Tissue and Gene Therapy Network, ThéCell, a thematic network supported by the Fonds de Recherche du Québec-Santé (Quebec Health Research Fund).