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

• Published in: The Prostate Vol. 67; no. 4; pp. 348 - 360
• Main Authors: Gao, Jin, Collard, Rachael L., Bui, Loan, Herington, Adrian C., Nicol, David L., Clements, Judith A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2007; Wiley-Liss
• Subjects: Biological and medical sciences; bone metastasis; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Cell Adhesion - physiology; Cell Communication - physiology; Cell Line, Tumor; Cell Movement - physiology; co-culture; Coculture Techniques; Gynecology. Andrology. Obstetrics; Humans; Kallikreins - genetics; Kallikreins - metabolism; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; prostate cancer; Prostate-Specific Antigen - metabolism; prostatic kallikreins; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; RNA, Messenger - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Andrology; Nephrology; Vasodilator agent; Prostate disease; Diseases of the osteoarticular system; co-culture; Osteoarticular system; Mixed cell culture; Plasma kallikrein; Osteoblast; Advanced stage; osteoblasts; Male genital diseases; Tumor cell; Urinary system disease; Serine endopeptidases; Enzyme; Gynecology; Interaction; Malignant tumor; Peptidases; Bone metastasis; prostatic kallikreins; Hydrolases; Mediator; Metastatic; Bone; Prostate cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20465

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. Prostate 67: 348–360, 2007. © 2007 Wiley‐Liss, Inc.