A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation
Open Access
- 19 May 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 27 (39), 5195-5203
- https://doi.org/10.1038/onc.2008.156
Abstract
ErbB3 is a transmembrane growth factor receptor that has been implicated in the pathogenesis of human cancer. After finding that a truncated form of ErbB3 was present and upregulated in metastatic prostate cancer cells in lymph nodes and bone, we explored the pathophysiological functions of this unusual form of ErbB3 in the context of mouse calvaria as well as osteoblasts in vitro and the femur microenvironment in vivo. Here we demonstrate that prostate cancer cells expressed an alternatively spliced transcript that encodes a 45-kDa glycosylated protein (p45-sErbB3). The recombinant p45-sErbB3 purified from conditioned medium stimulated calvarial bone formation and induced osteoblast differentiation. Overexpression of p45-sErbB3 in the osteolytic prostate cancer cell line PC-3 converted its phenotype from bone lysing to bone forming upon injection into the femurs of immunodeficient mice. Further, we detected sErbB3 in plasma samples from patients with castration-resistant prostate cancer with bone metastasis. These observations establish that p45-sErbB3 is a structurally and functionally unique gene product of ErbB3 and suggest that p45-sErbB3 is likely one of the factors involved in the osteoblastic bone metastases of prostate cancer.Keywords
This publication has 20 references indexed in Scilit:
- Soluble ErbB3 Levels in Bone Marrow and Plasma of Men with Prostate CancerClinical Cancer Research, 2008
- A Secreted Isoform of ErbB3 Promotes Osteonectin Expression in Bone and Enhances the Invasiveness of Prostate Cancer CellsCancer Research, 2007
- The central role of osteoblasts in the metastasis of prostate cancerCancer and Metastasis Reviews, 2006
- 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
- Establishment and characterization of osseous prostate cancer models: Intra‐tibial injection of human prostate cancer cellsThe Prostate, 2002
- Heregulin-dependent Activation of Phosphoinositide 3-Kinase and Akt via the ErbB2/ErbB3 Co-receptorPublished by Elsevier BV ,2001
- INCIDENCE OF SKELETAL COMPLICATIONS IN PATIENTS WITH BONE METASTATIC PROSTATE CANCER AND HORMONE REFRACTORY DISEASE: PREDICTIVE ROLE OF BONE RESORPTION AND FORMATION MARKERS EVALUATED AT BASELINEJournal of Urology, 2000
- Ultrastructural analysis of bone nodules formed in vitro by isolated fetal rat calvaria cellsBone, 1988