A secreted isoform of ErbB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells.
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.
Chen
Nanyue
N
Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Ye
Xiang-Cang
XC
Chu
Khoi
K
Navone
Nora M
NM
Sage
E Helene
EH
Yu-Lee
Li-Yuan
LY
Logothetis
Christopher J
CJ
Lin
Sue-Hwa
SH
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms; D020893:Receptor, ErbB-3 / Q000096:biosynthesis* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
D015676:Osteonectin; D020033:Protein Isoforms; D011994:Recombinant Proteins; D020893:Receptor, ErbB-3