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Regulation of pericyte migration by Secreted Protein Acidic and Rich in Cysteine (SPARC)
Author(s) -
Rivera Lee Benjamin,
Brekken Rolf Andrew
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.830.7
Subject(s) - pericyte , immunoprecipitation , chemistry , microbiology and biotechnology , fibronectin , null cell , antibody , in vitro , cysteine , osteonectin , cell culture , cell migration , cell , endothelial stem cell , biology , immunology , biochemistry , gene , genetics , enzyme , alkaline phosphatase , osteocalcin
Pericyte recruitment is required for stabilization of blood vessels. We observed that orthotopic tumors grown in SPARC‐null mice exhibited a reduction in pericyte‐associated blood vessels compared to tumors grown in wildtype mice. These data implicate SPARC as a regulator of pericyte recruitment. To investigate how SPARC affects pericyte behavior we examined primary pericytes isolated from wildtype and SPARC‐null animals and 10T1/2 cells in vitro. Using a transwell assay, we found that reduction of SPARC activity by the use of RNAi or a neutralizing antibody reduced the migration of 10T1/2 cells towards fibronectin. Additionally, we found that pericytes isolated from SPARC‐null mice migrated significantly less than wildtype counterparts. Treatment with a TGFβ neutralizing antibody or an ALK5 inhibitor abrogated these effects. Furthermore, we found that SPARC interacts with endoglin as demonstrated by coimmunoprecipitation and solid phase binding assays. Finally, we determined that endoglin expression is required for SPARC to effect pericyte migration. These data suggest that SPARC functions through endoglin to control TGFβ‐mediated inhibition of pericyte migration. Funding was provided by RO1CA118240.