Clinical Cancer Research, Vol 1, Issue 8 899-906, Copyright © 1995 by American Association for Cancer Research

ARTICLES

Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastases

ZS Zeng, AM Cohen, ZF Zhang, W Stetler-Stevenson and JG Guillem
Colorectal Service, Department of Surgery and Epidemiology Service, Department of Epidemiology and Statistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Tissue inhibitor of metalloproteinase (TIMP) inhibits the proteolytic activity of several matrix metalloproteinases centrally involved in tumor invasion and metastases. The purpose of this study was to determine the origin of TIMP-1 mRNA production in both human colorectal cancer (CRC) and metastatic liver lesions as well as define the relationships between TIMP-1 RNA expression and standard clinicopathological variables of CRC. Total cellular RNA, extracted from 56 CRC and 10 liver metastases, were examined by Northern blot hybridization. The mean/normal mucosa fold increase of TIMP-1 RNA was significantly elevated in both CRC (12.1 +/- 1.7) and liver metastases (10.0 +/- 3.6). No relationship was noted between TIMP-1 expression and tumor size, location nor differentiation. Based on lymph node metastases status, significantly higher TIMP-1 RNA levels were found in CRC with metastases than in those without metastases (15.6 +/- 3.3 versus 7.9 +/- 1.3) (P = 0.04). Similarly, TIMP-1 RNA levels were higher in primary CRC with distant metastases than those without distant metastases (17.6 +/- 4.1 versus 9.3 +/- 1.9) (P = 0. 04). In situ hybridization localized TIMP-1 mRNA predominantly in tumor stroma within spindle fibroblast-like cells rather than in cancer cells themselves. The correlation between the increased TIMP-1 mRNA level and advanced CRC stage noted in this study reflects a possible growth-promoting function for TIMP-1 in human CRC.

This article has been cited by other articles:

				A. Lipton, K. Leitzel, H. A. Chaudri-Ross, D. B. Evans, S. M. Ali, L. Demers, P. Hamer, S. Brown-Shimer, K. Pierce, V. Gaur, et al. Serum TIMP-1 and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen in Metastatic Breast Cancer J. Clin. Oncol., June 1, 2008; 26(16): 2653 - 2658. [Abstract] [Full Text] [PDF]

				L. Guedez, A. Martinez, S. Zhao, A. Vivero, S. Pittaluga, M. Stetler-Stevenson, M. Raffeld, and W. G. Stetler-Stevenson Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis of plasmacytic/plasmablastic tumors Blood, February 15, 2005; 105(4): 1660 - 1668. [Abstract] [Full Text] [PDF]

				S. Curran, S. R. Dundas, J. Buxton, M. F. Leeman, R. Ramsay, and G. I. Murray Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Phenotype Identifies Poor Prognosis Colorectal Cancers Clin. Cancer Res., December 15, 2004; 10(24): 8229 - 8234. [Abstract] [Full Text] [PDF]

				M. Yamazaki, T. Akahane, T. Buck, H. Yoshiji, D. E. Gomez, D. J. Schoeffner, E. Okajima, S. R. Harris, O. R. Bunce, S. S. Thorgeirsson, et al. Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice Carcinogenesis, September 1, 2004; 25(9): 1735 - 1746. [Abstract] [Full Text] [PDF]

				I. S. Aljada, N. Ramnath, K. Donohue, S. Harvey, J. J. Brooks, S. M. Wiseman, T. Khoury, G. Loewen, H. K. Slocum, T. M. Anderson, et al. Upregulation of the Tissue Inhibitor of Metalloproteinase-1 Protein Is Associated With Progression of Human Non-Small-Cell Lung Cancer J. Clin. Oncol., August 15, 2004; 22(16): 3218 - 3229. [Abstract] [Full Text] [PDF]

				R. Aalinkeel, M. P. N. Nair, G. Sufrin, S. D. Mahajan, K. C. Chadha, R. P. Chawda, and S. A. Schwartz Gene Expression of Angiogenic Factors Correlates with Metastatic Potential of Prostate Cancer Cells Cancer Res., August 1, 2004; 64(15): 5311 - 5321. [Abstract] [Full Text] [PDF]

				C. E. Schmalbach, D. B. Chepeha, T. J. Giordano, M. A. Rubin, T. N. Teknos, C. R. Bradford, G. T. Wolf, R. Kuick, D. E. Misek, D. K. Trask, et al. Molecular Profiling and the Identification of Genes Associated With Metastatic Oral Cavity/Pharynx Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, March 1, 2004; 130(3): 295 - 302. [Abstract] [Full Text] [PDF]

				G. C. Durkan, J. E. Nutt, P. H. Rajjayabun, D. E. Neal, J. Lunec, and J. K. Mellon Prognostic Significance of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 in Voided Urine Samples from Patients with Transitional Cell Carcinoma of the Bladder Clin. Cancer Res., November 1, 2001; 7(11): 3450 - 3456. [Abstract] [Full Text] [PDF]

				Y. Jiang, M. Wang, M. Y. Çeliker, Y. E. Liu, Q. X. Amy Sang, I. D. Goldberg, and Y. E. Shi Stimulation of Mammary Tumorigenesis by Systemic Tissue Inhibitor of Matrix Metalloproteinase 4 Gene Delivery Cancer Res., March 1, 2001; 61(6): 2365 - 2370. [Abstract] [Full Text]

				H. Yamamoto, F. Itoh, S. Iku, Y. Adachi, H. Fukushima, S. Sasaki, M. Mukaiya, K. Hirata, and K. Imai Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Human Pancreatic Adenocarcinomas: Clinicopathologic and Prognostic Significance of Matrilysin Expression J. Clin. Oncol., February 15, 2001; 19(4): 1118 - 1127. [Abstract] [Full Text] [PDF]

				M. Hidalgo and S. G. Eckhardt Development of Matrix Metalloproteinase Inhibitors in Cancer Therapy J Natl Cancer Inst, February 7, 2001; 93(3): 178 - 193. [Abstract] [Full Text] [PDF]

				M. N. Holten-Andersen, R. W. Stephens, H. J. Nielsen, G. Murphy, I. J. Christensen, W. Stetler-Stevenson, and N. Brunner High Preoperative Plasma Tissue Inhibitor of Metalloproteinase-1 Levels Are Associated with Short Survival of Patients with Colorectal Cancer Clin. Cancer Res., November 1, 2000; 6(11): 4292 - 4299. [Abstract] [Full Text] [PDF]

				G. Li, R. Fridman, and H.-R. C. Kim Tissue Inhibitor of Metalloproteinase-1 Inhibits Apoptosis of Human Breast Epithelial Cells Cancer Res., December 1, 1999; 59(24): 6267 - 6275. [Abstract] [Full Text] [PDF]

				M. Michael, B. Babic, R. Khokha, M. Tsao, J. Ho, M. Pintilie, K. Leco, D. Chamberlain, and F. A. Shepherd Expression and Prognostic Significance of Metalloproteinases and Their Tissue Inhibitors in Patients With Small-Cell Lung Cancer J. Clin. Oncol., June 1, 1999; 17(6): 1802 - 1802. [Abstract] [Full Text] [PDF]

				G Cox, W P Steward, and K J O'Byrne The plasmin cascade and matrix metalloproteinases in non-small cell lung cancer Thorax, February 1, 1999; 54(2): 169 - 179. [Full Text]

				P D BROWN Matrix metalloproteinases in gastrointestinal cancer Gut, August 1, 1998; 43(2): 161 - 163. [Full Text] [PDF]