Identification of fibulin-1 as a human bone marrow stromal (HS-5) derived factor that induces prostate cancer cell death
Date
2015
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Previous studies showed that HS-5 cells secret unidentified factor(s) inducing PCa cell death. Herein, the HS-5 derived factor (HS-5 DF) was characterized and identified. HS-5 DF had protein characteristics being trypsin and heat sensitive, but pH stable. The tentative size of the factor fell between 30 kDa and 100 kDa. Disulfide bonding was important for HS-DF activity. TGF-?1 treatment led to a suppression of HS-5 DF activity, a property consistent with bone metastasis in prostate cancer. Examination of TGF-?1 down regulated proteins in HS-5 cell CM lead to identification of fibulin-1 as a candidate for the DF. Immunoprecipitation of fibulin-1 from HS-5 CM and CRISPR knockdown of Fibulin-1 showed a significant reduction of HS-5 CM derived PCa cell death. These results strongly support a role for fibulin-1 in HS-5 bone marrow stromal cell induction of PCa cell death.