Stromal cells positively and negatively modulate the growth of cancer cells: stimulation via the PGE2-TNFα-IL-6 pathway and inhibition via secreted GAPDH-E-cadherin interaction

PloS One
Manabu KawadaAkio Nomoto

Abstract

Fibroblast-like stromal cells modulate cancer cells through secreted factors and adhesion, but those factors are not fully understood. Here, we have identified critical stromal factors that modulate cancer growth positively and negatively. Using a cell co-culture system, we found that gastric stromal cells secreted IL-6 as a growth and survival factor for gastric cancer cells. Moreover, gastric cancer cells secreted PGE2 and TNFα that stimulated IL-6 secretion by the stromal cells. Furthermore, we found that stromal cells secreted glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Extracellular GAPDH, or its N-terminal domain, inhibited gastric cancer cell growth, a finding confirmed in other cell systems. GAPDH bound to E-cadherin and downregulated the mTOR-p70S6 kinase pathway. These results demonstrate that stromal cells could regulate cancer cell growth through the balance of these secreted factors. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy.

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Citations

Sep 9, 2015·Mediators of Inflammation·Luciana Boffoni GentileDenise Fecchio
Jun 2, 2016·The Journal of Antibiotics·Tilman Schneider-PoetschHiroyuki Osada
May 7, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Siyuan SongPeng Shu

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Methods Mentioned

BETA
xenograft
gel filtration
electrophoresis
antibody array
PCR
fluorescence microscopy
confocal microscopy
transfection

Software Mentioned

FluoView

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