Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue andorgan cultured prostate tissue: Levels of collagenolytic and gelatinolyticMMPs are low, variable and different in fresh tissue versus organ-culturedtissue

Prostate tissue was obtained from 22 radical prostatectomies (performed for clinical management of prostate carcinoma) immediately after surgery. A sm all piece of tissue was fixed immediately in formalin and used for routine histology while a second piece was frozen in OCT and used for immuno-histoc hemistry. Another small piece was used for isolation of epithelial and stro mal cells. The remainder of the tissue was cut into 2 x 2 mm pieces and inc ubated in organ culture for 8 days. In organ culture, non-malignant, basal epithelial cells underwent a proliferative response. This was accompanied b y de-differentiation of glandular structures and by migration of epithelial cells across the surface of the tissue. Erosion of the basement membrane c ould also be seen in places, but was not widespread. Invasion of epithelial cells into the adjacent stroma was not evident. Production of matrix metal loproteinases (MMPs) with gelatinolytic activity or collagenolytic activity was assessed in organ culture and compared to expression patterns in fresh tissue. MMP-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) w ere undetectable or low in fresh tissue specimens. Both enzymes were detect ed in organ culture and both increased over time. Even after 6 days, howeve r, there was only a low level of gelatin-hydrolytic activity and no measura ble collagen-hydrolytic activity. In past studies we used organ cultures of normal skin and malignant skin tumours (basal cell carcinomas) to help elu cidate the role of collagenolytic and gelatinolytic MMPs in epithelial cell invasion (Varani et al, 2000). Compared to MMP levels observed in skin, le vels of these enzymes in prostate are low. The low level of collagenolytic and gelatinolytic MMPs in fresh prostate tissue and in organ-cultured prost ate tissue may help explain why there is little tissue destruction in many primary prostate tumours and why the majority of such tumours remain confin ed to the prostate for extended periods. (C) 2001 Cancer Research Campaign.