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| INHIBITION OF ORGAN INVASION BY THE MATRIX METALLOPROTEINASE INHIBITOR BATIMASTAT (BB-94) IN 2 HUMAN COLON-CARCINOMA METASTASIS MODELS |
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| Author(s): WATSON SA, MORRIS TM, ROBINSON G, CRIMMIN MJ, BROWN PD, HARDCASTLE JD |
| Source: CANCER RESEARCH Volume: 55 Issue: 16 Pages: 3629-3633 Published: AUG 15 1995 |
| Times Cited: 140 References: 18 |
| Abstract: The effect of the matrix metalloproteinase inhibitor batimastat was evaluated in two human colorectal cancer metastasis models involving: (a) the liver-invasive tumor C170HM(2) and (b) the lung-invasive tumor AP5LV, both of which have been shown to express the M(r) 72,000 type TV collagenase. Batimastat at concentrations between 0.01 and 3.0 mu g/ml had no direct cytotoxic effects on the in vitro growth of the cell lines. In the liver-invasive tumor model, batimastat administered i.p. from day 10 to termination of the therapy (day 39) at 40 mg/kg reduced both the mean number of liver tumors (35% of vehicle-treated control; P < 0.05) and the cross-sectional area of the tumors (43% of vehicle-treated control; P < 0.05). In the lung-invasive tumor model, batimastat administered daily (40 mg/kg i.p.) significantly reduced tumor weight within the lung (72% of vehicle-treated control; P < 0.05) but did not significantly affect nodule number. In the latter model, in which the take rate was unaffected, tumor cells were introduced into the lateral tail vein, and lung localization may have been a physical phenomenon not involving invasion. In the former model, tumor cells were introduced directly into the peritoneal cavity, and from there the cells adhered to and invaded the liver capsule. Because the take rate is significantly reduced, it may be that the matrix metalloproteinases are involved in this process. Batimastat may be a therapeutic modality for the treatment of colorectal cancer metastasis. |
| Document Type: Article |
| Language: English |
| Reprint Address: WATSON, SA (reprint author), UNIV NOTTINGHAM HOSP, QUEENS MED CTR, DEPT SURG, CANC STUDIES UNIT, NOTTINGHAM NG7 2RD, ENGLAND |
Addresses:
1. UNIV NOTTINGHAM HOSP, QUEENS MED CTR, DEPT PATHOL, NOTTINGHAM NG7 2RD, ENGLAND
2. BRITISH BIOTECH PHARMACEUT LTD, OXFORD OX4 5LY, ENGLAND |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: RN654 |
| ISSN: 0008-5472 |
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