title: Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastases.
abstract: The matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are perceived as essential for tumour invasion and metastasis. In the present study, we compare the topographical pattern of MMP-9 and TIMP-1 expression in colorectal cancer and liver metastasis by in situ hybridisation. TIMP-1 mRNA was detected in all 26 colorectal cancers examined, while only 18 out of 26 (69.2%) were positive for MMP-9. Both MMP-9 and TIMP-1 mRNA were observed in all ten liver metastases but were absent in three adenomas and in all normal colonic mucosa and liver. There was no association between MMP-9 or TIMP-1 mRNA expression and degree of differentiation or size of Tumours. MMP-9 and TIMP-1 mRNA were similarly observed in the peritumour stroma cells rather than in tumour cells themselves. MMP-9 mRNA positive cells were round and identified as macrophages by immunostaining with an anti-macrophage antibody (KP1), while TIMP-1, mRNA was detected in spindle-shaped stromal cells. In liver metastases, MMP-9 localised within peritumour stroma or at the interface between the tumour stroma and normal liver, whereas TIMP-1 mRNA was located throughout the malignant tumour stroma. Our data demonstrate a distinct pattern of MMP-9 and TIMP-1 mRNA expression in colorectal cancer and liver metastases suggesting distinct cellular origins as well as separate patterns of regulation.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zeng
authors.forename: J G
authors.initials: JG
authors.lastname: Guillem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary*; D008297:Male; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D020780:Matrix Metalloproteinase 9