Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer.
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.
Gao
Jin
J
Prostate Cancer Research Program, School of Life Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Collard
Rachael L
RL
Bui
Loan
L
Herington
Adrian C
AC
Nicol
David L
DL
Clements
Judith A
JA
D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D007610:Kallikreins; C120801:kallikrein 4; D017430:Prostate-Specific Antigen