Meta- y orto-tirosina: Estudio de sus efectos antimetastásicos en un modelo de adenocarcinoma mamario murino (LMM3)

MONTAGNA, DANIELA R.; DRAN, GRACIELA; CHIARELLA, PAULA; RUGGIERO, RAÚL A.; STRAZZA, ARIEL R.; MEISS, ROBERTO P.

Buenos Aires

Jornada; XXXI Jornadas multidisciplinarias de Oncología del Instituto Roffo; 2016

Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhibits or retards the growth of secondary tumor implants and metastases. Although previous studies have indicated that T-cell dependent mechanisms  mediate CR associated with immunogenic small tumors, the most universal manifestation of CR  induced by immunogenic and non-immunogenic large tumors had been associated with an antitumor serum factor that remained an enigma for many years. In a recent paper, we identified that elusive factor(s) as a mixture of meta-tyrosine (m-tyr) and ortho-tyrosine (o-tyr), two isomers of tyrosine that are not present in normal proteins. In this work, we have demonstrated that both m-tyr and o-tyr not only inhibited the in vivo and in vitro proliferation of tumor cells from tumors that induce CR as previously reported, but also that of tumor cells from a tumor (called LMM3) that does not induce CR and behave as highly metastatic one. We achieved this aim by demonstrating that a periodic intravenous administration of m-tyr and o-tyr induced a dramatic reduction of lung, hepatic and regional lymph node metastases generated in mice bearing-LMM3 tumor and decreased the rate of death and prolonged the survival time in LMM3 tumor-excised mice that already exhibited established metastases at the time of surgery. These anti-metastatic effects were achieved even at very low concentrations and without displaying any detectable toxic-side effects, suggesting that the use of m-tyr and o-tyr may help to develop new and less harmful means of managing malignant diseases, especially those aimed to control the growth of metastases that is considered the most serious problem in cancer pathology.