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A secreted isoform of ErbB3 promotes osteomectin expression in bone

ABSTRACT: The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interaction between prostate cancer cells and bone are critical for the preferential metastasis of PCa to bone. We previous identified a secreted isoform of ErbB3 (p45-sErbB3) from the bone marrow supernatants of patients with prostate cancer and bone metastasis. Immunohistochemical analysis of p45-sErbB3 expression in human specimens showed that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here we show that p45-sErbB3 stimulates calvarial bone to secrete factors that increase the invasiveness of prostate cancer cells in Boyden chamber invasion assay. We used gene array analysis to identify p45-sErbB3 regulated osteoblast genes that may enhance the invasiveness of PC-3 cells and found that p45-sErbB3 stimulated the expression of osteonectin, biglycan, and type I collagen in mouse calvaria. We further showed that recombinant osteonectin increases the invasiveness of PC-3 cells and osteonectin neutralizing antibody blocked p45-sErbB3 mediated invasiveness. These results suggest that p45-sErbB3 enhances the invasiveness of PC-3 cells is due, at least in part, to the stimulation of the secretion of osteonectin from bone. Thus, p45-sErbB3 mediates the bi-directional interaction between PCa cells and bone through osteonectin. Keywords: Prostate cancer, bone metastasis, P45-sErbB3, osteonectin

ORGANISM(S): Mus musculus

PROVIDER: GSE8001 | GEO | 2008/05/01

SECONDARY ACCESSION(S): PRJNA100789

REPOSITORIES: GEO

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A secreted isoform of ErbB3 promotes osteomectin expression in bone

Project description:The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interaction between prostate cancer cells and bone are critical for the preferential metastasis of PCa to bone. We previous identified a secreted isoform of ErbB3 (p45-sErbB3) from the bone marrow supernatants of patients with prostate cancer and bone metastasis. Immunohistochemical analysis of p45-sErbB3 expression in human specimens showed that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here we show that p45-sErbB3 stimulates calvarial bone to secrete factors that increase the invasiveness of prostate cancer cells in Boyden chamber invasion assay. We used gene array analysis to identify p45-sErbB3 regulated osteoblast genes that may enhance the invasiveness of PC-3 cells and found that p45-sErbB3 stimulated the expression of osteonectin, biglycan, and type I collagen in mouse calvaria. We further showed that recombinant osteonectin increases the invasiveness of PC-3 cells and osteonectin neutralizing antibody blocked p45-sErbB3 mediated invasiveness. These results suggest that p45-sErbB3 enhances the invasiveness of PC-3 cells is due, at least in part, to the stimulation of the secretion of osteonectin from bone. Thus, p45-sErbB3 mediates the bi-directional interaction between PCa cells and bone through osteonectin. Sample 1: non-treated calvaria RNA, Group 1 Sample 2: sErbB3 (100ng/ml) treated calvaria RNA, Group 2 Array: GE-supper array MM026 (total 96 genes, with 10 housekeeping genes) (service from SuperArray Bioscience Corporation: http://www.superarray.com

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