engleski

Bone morphogenetic proteins and their receptors in prostate cancer pathogenesis

Prostate cancer is highly spread malignancy in male population. Further, osteoblastic bone metastases are common in advanced prostate cancer but the mechanisms by which tumor cells stimulate new bone formation remain unclear. Bone morphogenetic proteins (BMPs) are growth factors produced by prostate cancer and stimulate osteoblast proliferation. Recent research showed that BMPs are expressed in normal and malignant prostatic tissue. BMPs signal through an interaction with BMP membrane receptors (BMPRs) type I and type II. It was shown that well-differentiated cancers were positive for the expression of BMPR II, BMPR-IA and BMPR-IB in contrast to poorly differentiated prostatic cancers which were negative for each of the three BMPRs, So, BMPs can be potential regulators of prostatic cancer cell growth and metastasis. We have investigated the expression of some BMPs and their membrane receptors in differently prostatic cancer tissue with or without metastasis as well as in benign prostatic hyperplasia. Immunohistochemical analysis of BMP-2/4, -3, -5, -6, -7 and BMPR-IA, BMPR-IB and BMPR-II were carried out in 31 patients with diagnosed prostatic cancer. Twenty-one patients had multiple bone metastases proven by bone scan. Three bone metastases had corresponding primary prostate cancer tissue. Other 10 patients had no skeletal metastasis and prostatic tissue sections containing prostatae cancer and associated benign prostatic hyperplasia (BPH). In non-metastatic prostate carcinoma the ewpression of all BMPs is rather similar to normal prostate tissue excerpt BMP-7 which is lower positive in carcinoma tissue. In prostate carcinoma with bone metastases the expression of BMP-6 and – 7 was significantly less positive. In normal prostate, BMPRs were localized predominantly to epithelial cells. In prostate cancer samples with proved bone metastases the expression of three receptors was significantly changed and very low. That can be seen especially for BMPR-II which expression was almost negative. The bone metastatic tissue, patohistological analysis proved as osteoblastic nature, showed significantly higher expression of BMP-6, -7 and three receptors in contrast to prostate cancer tissue of the same patients. So, we can see loss of BMPRs expression in primary cancer tissue after developing of bone metastases.

bone morphogenetic proteins; BMP-receptors; prostate cancer; bone metastases

DOI: 10.1007/s00223-006-6003-y