The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPS) in metastatic colorectal cancer (CRC)
The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPS) in metastatic colorectal cancer (CRC)
The expression pattern of MMPs (Collagenases MMPs 1,8,13; Gelantinases MMPs 2,9; Stromelysins MMPs 3,7) and TIMPs (TIMPs 1 and 2) was examined in fresh tissue and paraffin sections from 30 patients undergoing hepatic resection for colorectal carcinoma metastases and 3 patients with benign liver lesions, using semiquantitative RT-PCR and immunohistochemistry. It was also examined, using immunohistochemistry, in the paraffin sections of the primary tumours giving rise to these liver metastases.
MMP 1, MMP 9, MMP 3 and MMP 7 mRNAs were highly expressed in colorectal liver metastases. Immunohistochemistry confirmed these findings, MMPs 1 and 9 being expressed by tumour stromal cells, whereas MMPs 3 and 7 were expressed by adeenocarcinoma and stromal cells. TIMP 1 and TIMP 2 mRNA was expressed by both colorectal carcinoma metastases and distal liver. The expression of TIMP 1 and 2 mRNA in the adjacent liver was markedly lower than in both the metastasis and distal liver. In the benign lesions TIMP 1 and 2 mRNA expression appeared equal throughout. All the primary tumours MMP 1,8,2,9,3,7 and TIMP 1 and 2. Tumour stromal cells expressed MMP 1 (fibroblasts and macrophages), MMP 8 (fibroblasts), MMP 2 (fibroblasts), MMP 9 (macrophages). MMPs 3 and 7 were expressed by both adenocarcinoma cells and tumour stromal macrophages. TIMP 1 was expressed by macrophages in the tumour stroma and TIMP 2 by fibroblasts.
High expression of MMPs 1,9,3 and 7 in the CRC metastasis and down regulation of TIMP 1 and 2 in the immediate adjacent liver tissue may facilitate local growth of hepatic metastatic disease. Further studies are required to elucidate the mechanisms involved in this complex relationship between metastasis liver, MMP and TIMP.
University of Southampton
Kelly, Stephen Richard
2b5e8a9e-bdc3-46e0-bf50-72be3a62bd51
2003
Kelly, Stephen Richard
2b5e8a9e-bdc3-46e0-bf50-72be3a62bd51
Kelly, Stephen Richard
(2003)
The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPS) in metastatic colorectal cancer (CRC).
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The expression pattern of MMPs (Collagenases MMPs 1,8,13; Gelantinases MMPs 2,9; Stromelysins MMPs 3,7) and TIMPs (TIMPs 1 and 2) was examined in fresh tissue and paraffin sections from 30 patients undergoing hepatic resection for colorectal carcinoma metastases and 3 patients with benign liver lesions, using semiquantitative RT-PCR and immunohistochemistry. It was also examined, using immunohistochemistry, in the paraffin sections of the primary tumours giving rise to these liver metastases.
MMP 1, MMP 9, MMP 3 and MMP 7 mRNAs were highly expressed in colorectal liver metastases. Immunohistochemistry confirmed these findings, MMPs 1 and 9 being expressed by tumour stromal cells, whereas MMPs 3 and 7 were expressed by adeenocarcinoma and stromal cells. TIMP 1 and TIMP 2 mRNA was expressed by both colorectal carcinoma metastases and distal liver. The expression of TIMP 1 and 2 mRNA in the adjacent liver was markedly lower than in both the metastasis and distal liver. In the benign lesions TIMP 1 and 2 mRNA expression appeared equal throughout. All the primary tumours MMP 1,8,2,9,3,7 and TIMP 1 and 2. Tumour stromal cells expressed MMP 1 (fibroblasts and macrophages), MMP 8 (fibroblasts), MMP 2 (fibroblasts), MMP 9 (macrophages). MMPs 3 and 7 were expressed by both adenocarcinoma cells and tumour stromal macrophages. TIMP 1 was expressed by macrophages in the tumour stroma and TIMP 2 by fibroblasts.
High expression of MMPs 1,9,3 and 7 in the CRC metastasis and down regulation of TIMP 1 and 2 in the immediate adjacent liver tissue may facilitate local growth of hepatic metastatic disease. Further studies are required to elucidate the mechanisms involved in this complex relationship between metastasis liver, MMP and TIMP.
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Published date: 2003
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Local EPrints ID: 465469
URI: http://eprints.soton.ac.uk/id/eprint/465469
PURE UUID: 4cb3837a-e42f-4f2d-92d5-d78f7f545419
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Date deposited: 05 Jul 2022 01:14
Last modified: 16 Mar 2024 20:12
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Stephen Richard Kelly
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