The overall objective of this research is to identify the mechanism(s) whereby dietary restriction of tyrosine and phenylalanine blocks spuntaneous hematogerous metastasis in a variety of rodent neoplasms. The proposed research would complement ongoing clinical trials evaluating the diet as an adjuvant therapy for meloanoma patients. Our preliminary results indicate that this amino acid restriction alters the phenotype of the highly invasive and metastatic B16BL6 melanoma cell line such that it becomes defective in a required invasive function. The major thrust of the proposed research will be to characterize the nature of the induced dietary modulation in variants isolated from lymph node and lung metastases. The extent of the modulation will be assessed by examining tumor cell phenotypes of known importance to the metastatic cascade: the ability of tumor cells to attach to, degrade, and invade through extracellular matrices, and their ability to survive and establish colonies in the lung after intravenous inoculation. We will define the stability of the dietinduced modulation in both in vivo and in vitro environments, and will determine the level of tyrosine and phenyklalanine necessary to block spontaneous hematogenous metastatis of the dietmodified tumor cell variants.
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