Increased matrix stiffness suppresses ATP-induced sustained Ca2+ influx in MDA-MB-231 breast cancer cells. (June 2022)

• Record Type: Journal Article
• Authors: So, Choon Leng; Meinert, Christoph; Xia, Qing; Robitaille, Mélanie; Roberts-Thomson, Sarah J; Monteith, Gregory R
• Is Part Of: Cell calcium. Volume 104(2022)
• Publication Date: 2022-06
• Subjects: Breast cancer -- Matrix stiffness -- Calcium signaling -- ORAI1 -- FLIPR; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2022.102569
• Languages: English
• ISSNs: 0143-4160

Abstract

Highlights: Calcium remodeling can be assessed in cells on gel matrices of tunable stiffness. Stiffer matrices attenuate ATP-induced calcium influx in MDA-MB-231 cells. Remodeling of ATP-induced calcium responses by stiffer matrices is ORAI1-dependent. Abstract: Both matrix stiffening and remodeling of calcium signaling occur in breast cancers, with downstream consequences linked to the progression of the disease. However, the potential intersection between calcium signaling and matrix stiffness has not been fully assessed in models of cancer. Here, we describe the assessment of calcium signaling in breast cancer cells at high and low matrix stiffness using novel gel culture models (gelatin methacryloyl and polydimethylsiloxane) and MDA-MB-231 breast cancer cells expressing the calcium sensor GCaMP6m. Remodeling of ATP-stimulated cytosolic calcium responses in cells on different matrices was assessed using a high throughput fluorescence imaging plate reader. Our data reveal that matrices of higher stiffness attenuate ATP-induced sustained calcium influx in MDA-MB-231 breast cancer cells. This matrix-mediated attenuation of sustained calcium influx was dependent on the store-operated calcium channel component ORAI1. These studies suggest that calcium signaling in breast cancer cells can be altered as a consequence of matrix stiffness; modulation of such pathways may represent a new mechanism to target calcium signaling to regulate tumor progression in breast cancer. Graphical abstract: Image, graphical abstract