Thrombin: implications for intratumor therapy against metastasis.

The effect of an intratumor injection of thrombin as a potential cancer therapeutic agent was examined in two transplantable solid tumor models: a renal adenocarcinoma implanted beneath the kidney capsule in Wistar-Lewis rats and a rhabdomyosarcoma implanted similarly in Wag-Rij rats. For each tumor type, a group of test animals received a single dose of thrombin injected directly into the central tumor mass 6 weeks following tumor implantation. Corresponding groups of tumor-implanted controls consisted of animals that received an equal volume injection of saline instead of thrombin and animals that were not injected. The tumor-implanted animals receiving thrombin, saline, or no injection were handled identically. The saline-injected and noninjected control animals died of metastasis to the lung within the same well-defined period of time. All animals receiving thrombin showed significantly increased longevity, and the degree of increase was related to variations in tumor size at the time of injection. In every case, animal death was due to pulmonary metastasis verified at autopsy, but animals receiving thrombin therapy lived about 85% longer following tumor implantation than animals not receiving therapy.