COLOCALIZATION OF MATRIX METALLOPROTEINASE-9-MESSENGER-RNA AND PROTEIN IN HUMAN COLORECTAL-CANCER STROMAL CELLS

The matrix metalloproteinases (MMPs) are perceived as essential for tu mour invasion and metastases. The purpose of this study was to determi ne the expression and cellular localisation of the 92 kDa type IV coll agenase (MMP-9) protein and mRNA in human colorectal cancer (CRC). In CRC and matched normal mucosa specimens from 26 CRC patients, Northern blot hybridisation and Western blot analyses provide convincing evide nce that MMP-9 is expressed in greater quantities in CRC than in norma l tissue. The MMP-9 tumour to normal mucosa fold-increase (T/N) was 9. 7 +/- 7.1 (mean +/- s.d.) (P<0.001) for RNA and 7.1 +/- 3.9 (P<0.001) for protein. The sites of MMP-9 mRNA and protein synthesis were coloca lised in tumour stroma by in situ hybridisation and immunohistochemist ry in 26 CRC samples. Both MMP-9 mRNA and protein signals were stronge st in the population of stromal cells concentrated at the tumour-strom a interface of an invading tumour. Furthermore, MMP-9-positive cells w ere identified as macrophages using an antimacrophage antibody (KPl) i n serial sections from ten CRC samples. Given the persistent localisat ion of MMP-9-producing macrophages to the interphase between CRC and s urrounding stroma, our observations suggest that MMP-9 production is c ontrolled, in part, by tumour-stroma cell interactions. Further studie s are needed to determine the in vivo regulation of MMP-9 production f rom infiltrating peritumour macrophages.