Evidence for nutrient modulation of tumor phenotype: impact of tyrosine and phenylalanine restriction.

We have shown that Tyr and Phe restriction suppresses the malignant phenotype of the highly invasive and metastatic BL6 variant of B16 murine melanoma. Lung-colonizing abilities of Tyr- and Phe-modulated in vivo and in vitro variants of BL6 are inhibited following intravenous inoculation into mice fed normal diet. Although this antimetastatic effect of Tyr and Phe restriction is most likely not due to differences in attachment to endothelium, our data indicate that major impacts of Tyr and Phe restriction are at the level of the tumor, itself. Modulation of host immune responses, which in turn suppresses metastasis, does not appear to contribute significantly to the altered phenotype. Although numbers and function of T cells, mast cells, and NK cells are affected by Tyr and Phe restriction, they are not involved in the Tyr- and Phe-mediated suppression of tumor growth, metastasis, or angiogenesis. Our data do not rule out the importance of other host factors involved in the Tyr and Phe modulation of tumor phenotype. The outcome of this modulation results most likely from complex Tyr/Phe-tumor-host interactions.