A Secreted Isoform of ErbB3 Promotes Osteonectin Expression in Bone and Enhances the Invasiveness of Prostate Cancer Cells
- 15 July 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 67 (14), 6544-6548
- https://doi.org/10.1158/0008-5472.can-07-1330
Abstract
The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interactions between prostate cancer cells and bone are critical for the preferential metastasis of prostate cancer to bone. We identified previously a secreted isoform of ErbB3 (p45-sErbB3) in bone marrow supernatant samples from men with prostate cancer and bone metastasis and showed by immunohistochemical analysis of human tissue specimens that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here, we show that p45-sErbB3 stimulated mouse calvaria to secrete factors that increased the invasiveness of prostate cancer cells in a Boyden chamber invasion assay. Using gene array analysis to identify p45-sErbB3–responsive genes, we found that p45-sErbB3 up-regulated the expression of osteonectin/SPARC, biglycan, and type I collagen in calvaria. We further show that recombinant osteonectin increased the invasiveness of PC-3 cells, whereas osteonectin-neutralizing antibodies blocked this p45-sErbB3–induced invasiveness. These results indicate that p45-sErbB3 enhances the invasiveness of PC-3 cells in part by stimulating the secretion of osteonectin by bone. Thus, p45-sErbB3 may mediate the bidirectional interactions between prostate cancer cells and bone via osteonectin. [Cancer Res 2007;67(14):6544–8]Keywords
This publication has 20 references indexed in Scilit:
- Increased Expression of Osteopontin Contributes to the Progression of Prostate CancerCancer Research, 2006
- Expression of recombinant MDA-BF-1 with a kinase recognition site and a 7-histidine tag for receptor binding and purificationProtein Expression and Purification, 2005
- Osteoblasts in prostate cancer metastasis to boneNature Reviews Cancer, 2005
- Androgen-Independent Prostate Cancer Is a Heterogeneous Group of DiseasesCancer Research, 2004
- Up‐regulation of MDA‐BF‐1, a secreted isoform of ErbB3, in metastatic prostate cancer cells and activated osteoblasts in bone marrowThe Journal of Pathology, 2004
- Molecular Pathway for Cancer Metastasis to BoneJournal of Biological Chemistry, 2003
- Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implicationsCancer, 2003
- Role of Osteopontin in Cellular Signaling and Toxicant InjuryAnnual Review of Pharmacology and Toxicology, 2001
- Osteopenia and decreased bone formation in osteonectin-deficient miceJCI Insight, 2000
- Osteonectin, a bone-specific protein linking mineral to collagenCell, 1981