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Correlation of the osteoblastic phenotype with prostate‐specific antigen expression in metastatic prostate cancer: implications for paracrine growth
Author(s) -
Doherty Alan,
Smith Gillian,
Banks Linda,
Christmas Timothy,
Epstein Richard J.
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199907)188:3<278::aid-path358>3.0.co;2-g
Subject(s) - paracrine signalling , prostate cancer , phenotype , prostate , prostate specific antigen , medicine , antigen , cancer research , oncology , cancer , biology , immunology , gene , genetics , receptor
The characteristic sclerotic appearance of bone metastases from prostate cancer is unexplained but could involve excess peritumoural activity of osteoblast mitogens such as the insulin‐like growth factors (IGFs). Since prostatic metastases are distinguished by androgen‐dependent secretion of prostate‐specific antigen (PSA), a serine protease which cleaves extracellular IGF‐binding proteins and thereby enhances the bioavailability of IGFs, the relationship was examined between tumour PSA expression and the osteoblastic phenotype. To this end, a cohort of 27 prostate cancer patients was evaluated to determine the relationship between serum PSA and radiographic bone lesion density at first presentation with metastatic disease. No linear correlation between absolute PSA levels and metastatic osteosclerosis was apparent. However, non‐parametric statistical analysis revealed a highly significant link between low‐PSA (<20 ng/ml) metastatic prostate cancer and osteolytic bone lesions ( p < 0·0001, χ 2 = 21·5). This finding raises the possibility that the osteoblastic phenotype of prostate cancer derives in part from PSA‐dependent proteolysis of IGF‐binding proteins within bone matrix. Copyright © 1999 John Wiley & Sons, Ltd.