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Exogenous thrombospondin‐1 induces a signal transduction modifying the LNCaP cell genotype from pro‐angiogenic to anti‐angiogenic: description of a potential mechanism of action
Author(s) -
CarpioCano Fabiola Elizabeth Del,
Murayi Roger B,
Ogunkua Lawrence A,
Safadi Fayez F.,
DeLa Cadena Raul A.
Publication year - 2007
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.21.6.a855-d
Subject(s) - lncap , thrombospondin 1 , angiogenesis , biology , autocrine signalling , signal transduction , cd36 , cancer research , microbiology and biotechnology , cell , cell growth , cell culture , cancer cell , receptor , cancer , biochemistry , genetics
The expression of CD36, a TSP1 receptor on the surface of LNCaP(prostate cancer cell line) allows cells to express TSP1 on their surface, to induce cell‐signaling, promote cell‐cell interaction and invasion. Recently, the TSP1 gene has been found to be up‐regulated on LNCaP cells. Despite a pronounced CD36 expression on LNCaP cells, TSP1 cell‐surface expression is low in contrast to the abundant TSP1 accumulation in the cytoplasm and perinuclear region. Thus, we investigated the mechanisms associated with over‐expression of the TSP1 gene. LNCaP cells in culture were exposed to exogenous TSP1 (1ug/ml) for 24 hrs prior to mRNA and protein extraction. Western‐blotting technique was utilized to visualize TSP1. By the use of Oligo GEArray for human angiogenesis, 120 genes were evaluated. Western‐blotting technique revealed a truncated form of TSP1 (68 kDa), which was not due to proteolytic fragmentation of the intact TSP1 molecule (180kDa). This finding may explain the lack of TSP1 cell‐surface expression and its accumulation in the cytoplasm of LNCaP cells. Thirty‐three up‐regulated related angiogenic genes including TGFB2, IL1b and PDGF were down‐regulated by exogenous TSP1, therefore shifting the genotype from pro‐ to anti‐angiogenic. These results suggest that CD36 signaling in response to TSP1 is intact and that targeting CD36 with TSP1 peptides may provide a potential therapeutic benefit in prostate cancer.