MODULATION OF B16-BL6 MURINE MELANOMA METASTATIC PHENOTYPE BY TYROSINE AND PHENYLALANINE RESTRICTION IN THE ABSENCE OF HOST SELECTION PRESSURES

We previously showed that restriction of tyrosine (Tyr) and phenylalan ine (Phe) in vivo dramatically suppresses the metastatic phenotype of B16-BL6 (BL6) murine melanoma. Present results indicate a direct effec t of Tyr and Phe restriction on the tumor in the absence of host selec tion pressures. Lung colonizing ability of BL6 is dramatically suppres sed after one passage in vitro in media containing low levels of Tyr a nd Phe. This antimetastatic effect is immediate, stable for at least 5 in vitro passages in Tyr and Phe restricted media, and evident even a fter levels of Tyr and Phe are restored to normal. Heterogeneity for l ung colonizing ability is suppressed, as evidenced by fewer tumor colo nies formed by clones following i. v. inoculation into mice fed normal diet. This suppression of BL6 metastatic phenotype is not due to diff erential clearance and retention in the lung or to decreased growth, b ut is specific for these two amino acids. As the mechanism(s) for the antitumor effects of Tyr and Phe restriction are detailed, the relevan ce of Tyr and Phe restriction as an early adjuvant to effective cancer treatment can be explored.