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Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis.

ABSTRACT: Angiogenesis requires tightly coordinated crosstalk between endothelial cells (ECs) and stromal cells, such as fibroblasts and smooth muscle cells. The specific molecular mechanisms moderating this process are still poorly understood.Stromal cell-derived factors are essential for EC sprouting and lumen formation. We therefore compared the abilities of 2 primary fibroblast isolates and a primary smooth muscle cell isolate to promote in vitro angiogenesis, and analyzed their secretomes using a combination of nano liquid chromatography-mass spectrometry/mass spectrometry, quantitative PCR, and ELISA. Each isolate exhibited a different level of angiogenic ability. Using quantitative MS, we then compared the secretomes of a fibroblast isolate exhibiting low angiogenic activity, a fibroblast isolate exhibiting high angiogenic activity, and human umbilical vein ECs. High angiogenic fibroblast supernatants exhibited an overabundance of proteins associated with extracellular matrix constituents compared with low angiogenic fibroblasts or ECs. Finally, small interfering RNA technology and purified protein were used to confirm a role for stromal cell-derived hepatocyte growth factor and fibronectin in inducing EC sprouting.Differences in stromal cell ability to induce angiogenesis are a result of differences in the secreted proteomes of both extracellular matrix proteins and proangiogenic growth factors.

SUBMITTER: Newman AC

PROVIDER: S-EPMC3638018 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis.

Newman Andrew C AC Chou Wayne W Welch-Reardon Katrina M KM Fong Ashley H AH Popson Stephanie A SA Phan Duc Thien DT Sandoval Daniel R DR Nguyen Dananh P DP Gershon Paul D PD Hughes Christopher C W CC

Arteriosclerosis, thrombosis, and vascular biology 20130103 3

<h4>Objective</h4>Angiogenesis requires tightly coordinated crosstalk between endothelial cells (ECs) and stromal cells, such as fibroblasts and smooth muscle cells. The specific molecular mechanisms moderating this process are still poorly understood.<h4>Methods and results</h4>Stromal cell-derived factors are essential for EC sprouting and lumen formation. We therefore compared the abilities of 2 primary fibroblast isolates and a primary smooth muscle cell isolate to promote in vitro angiogene ...[more]

PMID: 23288153

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Dataset Information

Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis.

Publications

Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis.

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