Increased type-IV collagenase (MMP-2 and MMP-9) activity following preoperative radiotherapy in rectal cancer

The aim of this study was to investigate the effect of preoperative high-do se radiotherapy (25 Gy in 5 fractions over 5 days) on the type-IV collagena se protein profile, in patients with resectable rectal cancer, by gelatin z ymography, Biopsy samples of tumour and distant normal mucosa from 12 patie nts with resectable rectal cancer were obtained pre- and post-radiotherapy. Expression of type-IV collagenases (both pro- and active forms) was studie d using gelatin zymography. Enzyme levels were normalized for total protein content of each sample. Rectal cancer specimens expressed both pro (72 kDa ) and active (62 kDa) forms of MMP-2 but only the pro form of MMP-9 (92 kDa ). Normal mucose showed expression of the pro forms of MMP-2 and MMP-9 whil e no active form of either enzyme was detected in any of the samples. A sig nificant three- to fourfold increase (P < 0.01) of active matrix metallopro teinases (MMP)-2 (62 kDa) was seen in malignant rectal mucosa after radioth erapy The effect of radiotherapy also led to a twofold increase (P = 0.047) of pro MMP-2 (72 kDa) and a two- to threefold increase (P = 0.03) of the p recursor form of MMP-9 (92 kDa). In contrast, in normal mucosa expression o f the precursor form of MMP-9 (92 kDa) did not change after radiation, and no significant effect on the levels of pro MMP-2 (72 kDa) was observed. Pre operative high-dose radiotherapy leads to an increase in activity of type-I V collagenases in patients with resectable rectal cancer. Type-IV collagena se inhibition may be a useful therapeutic adjunct to radiotherapy in rectal cancer. (C) 2000 Cancer Research Campaign.