Carcinogenesis, Vol. 20, No. 8, 1445-1452,
August 1999
© 1999 Oxford University Press
Cancer Biology |
Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats
Unité de Biologie et Pathologie de l'Epithélium Digestif INSERM Unité 10, IFR Cellules Epithéliales, Hôpital Bichat-Claude Bernard, 170 Boulevard NEY, Paris 75018, France
Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation which play a role in cancer progression and metastatic spreading. We investigated the effects of the MMP inhibitor, batimastat, in vitro on the proliferation and invasiveness of the rat colon cancer cell line DHD/K12, and in vivo on the growth of an aggressive model of peritoneal carcinomatosis producing haemorrhagic ascites and metastases, obtained in the rat by i.p. injection of DHD/K12 cells. MMP production was studied in conditioned culture media, solid tumors and ascitic fluid. In vivo, after injection of tumor cells on day 0, rats received i.p. daily either batimastat (30 mg/kg) or equal volume of vehicle from day 2 until killing on day 43 (series I) or from day 13 until death (series II). The grade of peritoneal carcinomatosis, ascite volume, number and size of liver metastases were evaluated in both series, and survival in series II. MMPs-1, -2 and -9 were identified in culture media, tumors and ascites. In vitro, batimastat did not modify DHD/K12 cell proliferation and slightly reduced cell invasion. In vivo, in series I, batimastat treatment totally prevented peritoneal carcinomatosis and liver metastasis development. In series II, it significantly prolonged survival (P < 0.0002) and reduced peritoneal carcinomatosis (P < 0.001) and hepatic metastases number as compared with controls. However, batimastat-treated rats of the two series had peritoneal inflammation with marked ascites. Nevertheless, inhibition of MMP is a new therapeutic approach which may be promising in treatment of microtumors as in more advanced cancer stages.
Abbreviations: MMPs, matrix metalloproteinases
1 To whom correspondence should be addressed Email: u10{at}bichat.inserm.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. GENTNER, A. WEIN, R. S. CRONER, I. ZEITTRAEGER, R. M. WIRTZ, F. ROEDEL, A. DIMMLER, L. DORLAQUE, W. HOHENBERGER, E. G. HAHN, et al. Differences in the Gene Expression Profile of Matrix Metalloproteinases (MMPs) and their Inhibitors (TIMPs) in Primary Colorectal Tumors and their Synchronous Liver Metastases Anticancer Res, January 1, 2009; 29(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Birkenkamp-Demtroder, S H Olesen, F B Sorensen, S Laurberg, P Laiho, L A Aaltonen, and T F Orntoft Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid Gut, March 1, 2005; 54(3): 374 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Wood and M. C. Archer Matrix Metalloproteinases-2 and 9 Do Not Play a Role in the Growth of Preneoplastic Liver Lesions in F344 Rats Experimental Biology and Medicine, September 1, 2001; 226(8): 799 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kermorgant, T. Aparicio, V. Dessirier, M. J.M. Lewin, and T. Lehy Hepatocyte growth factor induces colonic cancer cell invasiveness via enhanced motility and protease overproduction. Evidence for PI3 kinase and PKC involvement Carcinogenesis, July 1, 2001; 22(7): 1035 - 1042. [Abstract] [Full Text] [PDF]
|
|