Clinical Cancer Research, Vol 2, Issue 7 1207-1214, Copyright © 1996 by American Association for Cancer Research

ARTICLES

The matrix metalloproteinase inhibitor batimastat (BB-94) retards human breast cancer solid tumor growth but not ascites formation in nude mice

JA Low, MD Johnson, EA Bone and RB Dickson
Departments of Cell Biology, Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, D. C. 20007, and British Biotech, Ltd., Oxford OX4 5LY, United Kingdom.

Matrix metalloproteinases (MMPs) are thought to play a significant role in tumor invasion and metastasis as well as angiogenesis. Batimastat, also known as BB-94, acts as an inhibitor of metalloproteinase activity by binding the zinc ion in the active site of MMPs. In our study, the hormone-independent MDA435/LCC6 human breast cancer cell line was used to seed solid tumors s.c. into the region of the mammary fat pad in athymic nude mice. Mice were treated with 50 mg/kg batimastat i.p. Tumor volume measurements showed a statistically significant decrease in tumor size between batimastat-treated and control animals. In contrast, we also used the same MDA435/LCC6 cell line to propagate a malignant ascites in nude mice, which yielded a very different response to batimastat. Batimastat, in previously published literature, had been shown to prolong the life of mice bearing ovarian ascites tumors. Treatment with batimastat in our ascites model produced no increase in survival or significant suppression of ascites formation. However, treated animals showed dramatic tumor cell consolidation and less dispersed ascites cells compared with control animals. Two potential targets of batimastat, gelatinase A and B (MMP-2 and -9, respectively), were examined in both tumor sites. These metalloproteinases were present in both solid tumor and ascites fluid and in both cases were host derived and not produced by the tumor. We conclude that batimastat may have different effects on tumor progression and growth depending on the site of tumor implantation.

This article has been cited by other articles:

				B. Desai, T. Ma, and M. A. Chellaiah Invadopodia and Matrix Degradation, a New Property of Prostate Cancer Cells during Migration and Invasion J. Biol. Chem., May 16, 2008; 283(20): 13856 - 13866. [Abstract] [Full Text] [PDF]

				B. P. Schneider and K. D. Miller Angiogenesis of Breast Cancer J. Clin. Oncol., March 10, 2005; 23(8): 1782 - 1790. [Full Text] [PDF]

				K. D. Miller, C. J. Sweeney, and G. W. Sledge The Snark is a Boojum: the continuing problem of drug resistance in the antiangiogenic era Ann. Onc., January 1, 2003; 14(1): 20 - 28. [Abstract] [Full Text] [PDF]

				T. Sumii and E. H. Lo Involvement of Matrix Metalloproteinase in Thrombolysis-Associated Hemorrhagic Transformation After Embolic Focal Ischemia in Rats Stroke, March 1, 2002; 33(3): 831 - 836. [Abstract] [Full Text] [PDF]

				N. Aslam and C. R. Marino Malignant Ascites: New Concepts in Pathophysiology, Diagnosis, and Management Arch Intern Med, December 10, 2001; 161(22): 2733 - 2737. [Abstract] [Full Text] [PDF]

				R. Hoekstra, F.A.L.M. Eskens, and J. Verweij Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives Oncologist, October 1, 2001; 6(5): 415 - 427. [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]

				P.-P. H. Lee, J.-J. Hwang, G. Murphy, and M. M. Ip Functional Significance of MMP-9 in Tumor Necrosis Factor-Induced Proliferation and Branching Morphogenesis of Mammary Epithelial Cells Endocrinology, October 1, 2000; 141(10): 3764 - 3773. [Abstract] [Full Text] [PDF]

				T. Aparicio, S. Kermorgant, V. Dessirier, M. J.M. Lewin, and T. Lehy Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats Carcinogenesis, August 1, 1999; 20(8): 1445 - 1452. [Abstract] [Full Text] [PDF]

				A. Price, Q. Shi, D. Morris, M. E. Wilcox, P. M. A. Brasher, N. B. Rewcastle, D. Shalinsky, H. Zou, K. Appelt, R. N. Johnston, et al. Marked Inhibition of Tumor Growth in a Malignant Glioma Tumor Model by a Novel Synthetic Matrix MetalloproteinaseInhibitor AG3340 Clin. Cancer Res., April 1, 1999; 5(4): 845 - 854. [Abstract] [Full Text] [PDF]

				V. M. Macaulay, K. J. O'Byrne, M. P. Saunders, J. P. Braybrooke, L. Long, F. Gleeson, C. S. Mason, A. L. Harris, P. Brown, and D. C. Talbot Phase I Study of Intrapleural Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in the Treatment of Malignant Pleural Effusions Clin. Cancer Res., March 1, 1999; 5(3): 513 - 520. [Abstract] [Full Text] [PDF]