CONICET | Buscador de Institutos y Recursos Humanos

Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhibits or retards the growth of secondary tumor implants. The importance of the study of CR relies on its relevance to elucidate mechanisms of metastases control since metastases may be considered natural secondary tumor implants. Tyrosine isomers, in particular meta-tyrosine (m-Tyr), have been claimed to be mediators of CR and in previous reports we demonstrated that m-Tyr could inhibit the growth of established metastases from three murine metastatic mammary carcinomas. In this communication we evaluated whether this anti-metastatic effect could be extended to other murine tumors very refractory to other treatments: a highly metastatic spontaneous melanoma (B16) and a highly metastatic methylcholanthrene-induced fibrosarcoma (MC-HM). Both tumors growing subcutaneously generate lung metastases starting at day 15 after tumor inoculation with 1 x 105 cells. Mice bearing B16 or MC-HM tumors were divided into two groups at 18 days after tumor inoculation. One group (Experimental group) received a daily inoculation of m-Tyr (67mg/Kg/day) by the intravenous route for the following 21 days and the other group (Control) received saline. After that time, all mice were sacrificed and lung metastases counted. Metastases for B16 (median [range]): Experimental group: 14 [0-64], (n = 12). Control group: 43 [5-206], (n = 11]; p < 0.02. Metastases for MC-HM (median [range]: Experimental group: 4 [0-33], (n = 6). Control group: 54 [8-100], (n = 7); p < 0.01. In both tumor models, when total metastatic load (number of metastases x individual size) were compared the difference was strikingly greater than that observed by comparing number of metastases only. Our results demonstrated that m-Tyr can inhibit the growth of established metastases of very refractory tumors.