Evidence for the existence of an organ specific, androgen-independent pathway of progression in patients with metastatic prostate cancer

Abstract

Ample clinical and preclinical data support the central role of bone-epithelial interaction in the progression of prostate cancer. The clinical progression of prostate cancer has been partially attributed to a cascade of interactions between the cancer compartment and microenvironment compartments. The expression of prostate specific antigen (PSA) parallels the activity of the epithelial compartment of prostate cancer. However, the clinical study of the bone-epithelial interaction has been limited by the lack of accessible relevant human tissue for study. This study was designed (1) to assess the value of human bone marrow as a source of tissue to study the bone-epithelial interaction and (2) to determine whether bone marrow supernatant regulates the expression of PSA in a human prostate cancer cell line (LNCaP) in vitro. The acellular bone marrow supernatant derived from patients with prostate cancer with different degrees of tumor spread, hormonal status, and histology were assayed for their ability to induce PSA expression in a human LNCaP. The bone marrow supernatants were derived from 53 patients with prostate cancer (49 with adenocarcinoma and 4 with small cell carcinoma) and eight control patients, who had cancers in other sites. In addition, the match serum specimens derived from 25 of the study patients also had been assayed for its PSA inductivity. In addition to the comparison with “static” serum and BM concentration of PSA, the rate of significant PSA induction by clinical stage and hormonal status was assessed. Patients with androgen-independent disease had the highest rate of PSA-inducing ability. Only two patients (8%) had weak PSA-inducing ability from their serum (both with high volume disease) and none of the bone marrow supernatants derived from patients without prostate cancer or small cell carcinoma had inducing ability. No correlation between the static BM or serum PSA concentrations and the inducing ability was seen. These results indicate that PSA expression can be regulated by androgen-independent factors. The bone marrow supernatant of patients with prostate cancer has unique properties and is a valuable source of tissue for clinical study of the progression of prostate cancer. These preliminary data suggest that induction of PSA by bone marrow supernatant should be studied for its clinical utility as an assay for the interaction between the epithelial and bone compartments, and it supports the existence of androgen-independent pathways of PSA regulation by the bone marrow supernatant of patients with advanced prostate cancer. If confirmed, these findings would support the use of bone marrow supernatant to study the osseous specific progression of prostate cancer.