A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation

Oncogene. 2008 Sep 4;27(39):5195-203. doi: 10.1038/onc.2008.156. Epub 2008 May 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Bone Development / physiology*
  • Bone Neoplasms / secondary
  • Cell Line, Tumor
  • Culture Media, Conditioned
  • DNA Primers
  • Humans
  • Male
  • Mice
  • Osteoblasts / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • Receptor, ErbB-3 / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Culture Media, Conditioned
  • DNA Primers
  • RNA, Messenger
  • Receptor, ErbB-3