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| INHIBITION OF MURINE MELANOMA EXPERIMENTAL METASTASIS BY RECOMBINANT DESULFATOHIRUDIN, A HIGHLY SPECIFIC THROMBIN INHIBITOR |
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| Author(s): ESUMI N, FAN D, FIDLER IJ |
| Source: CANCER RESEARCH Volume: 51 Issue: 17 Pages: 4549-4556 Published: SEP 1 1991 |
| Times Cited: 106 References: 84 |
| Abstract: Recombinant desulfatohirudin (r-hirudin), a highly specific inhibitor of thrombin, was examined to determine whether it would inhibit production of experimental lung metastasis by B16-F10 melanoma cells. In in vitro assays using mouse plasma, the high level of procoagulant activity in B16-F10 cells was significantly inhibited by r-hirudin in a dose-dependent manner. From 15 to 120 min after s.c. administration into C57BL/6 mice, r-hirudin (10 mg/kg) markedly prolonged clotting time in a time course pattern that directly correlated with that of blood distribution of I-125-labeled r-hirudin. The production of experimental lung metastasis by B16-F10 cells was significantly inhibited by r-hirudin administered s.c. at time points ranging from 120 min before to 60 min after tumor cell inoculation with the most significant effects found in mice given r-hirudin 15 or 2 min before the i.v. injection of tumor cells. The organ distribution of [I-125]IdUrd-labeled tumor cells demonstrated a clear difference in the lungs of mice treated with r-hirudin and the lungs. of control mice, and these differences directly correlated with the number of lung tumor colonies found 3 weeks later. The inhibition of lung metastasis was not due to direct antitumor effects of r-hirudin. These results suggest that inhibition of coagulation events by r-hirudin significantly inhibit experimental lung metastasis during a critical time of 60 min after the entry of tumor cells into the circulation. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT CELL BIOL, HMB 173, 1515 HOLCOMBE BLVD, HOUSTON, TX 77030 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: GC743 |
| ISSN: 0008-5472 |
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