Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer

Prostate. 2007 Mar 1;67(4):348-60. doi: 10.1002/pros.20465.

Abstract

Background: Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa.

Methods: Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays.

Results: hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4-transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV.

Conclusions: hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Cell Adhesion / physiology
  • Cell Communication / physiology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Coculture Techniques
  • Humans
  • Kallikreins / genetics
  • Kallikreins / metabolism*
  • Male
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger
  • Kallikreins
  • kallikrein 4
  • Prostate-Specific Antigen