INCREASED MATRIX METALLOPROTEINASE-9 SECRETION IN SHORT-TERM TISSUE-CULTURES OF PROSTATIC TUMOR-CELLS

We have examined the expression of 2 tumor-associated metalloproteinas es, MMP-2 and MMP-9, in 48 primary cultures of prostatic carcinoma (PR CA) and 33 cultures of benign prostatic hyperplasia (BPH). PRCA cultur es secrete significantly more MMP-9 than their benign counterparts. Se creted MMP-2 did not differ significantly in cultures but was lower in PRCA cultures. Two cultures of benign origin exhibited high MMP-9 sec retion and growth patterns consistent with a malignancy. Both cases we re followed and successively re-evaluated histologically and rediagnos ed as organ-confined PRCA. MMP expression in culture may be of predict ive value in the identification of incidental PRCA. MMP-9 secretion an d its ratio with MMP-2 were highest in epithelial cultures from invasi ve, metastatic tumors when compared both to disease confined to prosta te gland and to locally extensive disease. MMP-9 secretion was greates t also in cultures derived from tissues of high Gleason histological g rade. Active MMP-9 species were detected in 15 cultures (31%) of PRCA. Active MMP-2. species were observed in cultures of both BPH and PRCA origin in almost the same amounts. Although average levels were not si gnificantly different, as a ratio to preform species, a significant el evation was observed in cultures of PRCA origin. We propose, therefore , that an elevated expression of MMP-9 and a high ratio of MMP-9 to MM P-2 in short-term prostate epithelial cultures is of potential diagnos tic and prognostic significance. (C) 1996 Wiley-Liss, Inc.