Stanniocalcin-1 Regulates Extracellular ATP-Induced Calcium Waves in Human Epithelial Cancer Cells by Stimulating ATP Release from Bystander Cells |
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| Authors: | Gregory J Block Gabriel D DiMattia Darwin J Prockop |
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| Institution: | 1. Institute for Regenerative Medicine at Scott and White Hospital, Texas A&M Health Sciences Center, Temple, Texas, United States of America.; 2. London Regional Cancer Program and the Department of Oncology, Biochemistry, University of Western Ontario, London, Ontario, Canada.;University of Birmingham, United Kingdom |
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| Abstract: | BackgroundThe epithelial cell response to stress involves the transmission of signals between contiguous cells that can be visualized as a calcium wave. In some cell types, this wave is dependent on the release of extracellular trinucleotides from injured cells. In particular, extracellular ATP has been reported to be critical for the epithelial cell response to stress and has recently been shown to be upregulated in tumors in vivo.Methodology/Principal FindingsHere, we identify stanniocalcin-1 (STC1), a secreted pleiotrophic protein, as a critical mediator of calcium wave propagation in monolayers of pulmonary (A549) and prostate (PC3) epithelial cells. Addition of STC1 enhanced and blocking STC1 decreased the distance traveled by an extracellular ATP-dependent calcium wave. The same effects were observed when calcium was stimulated by the addition of exogenous ATP. We uncover a positive feedback loop in which STC1 promotes the release of ATP from cells in vitro and in vivo.Conclusions/SignificanceThe results indicated that STC1 plays an important role in the early response to mechanical injury by epithelial cells by modulating signaling of extracellular ATP. This is the first report to describe STC1 as a modulator or purinergic receptor signaling. |
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