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Tyrosine Isoforms Involved in Concomitant Tumor Resistance

Ortho- and meta-isoforms of tyrosine inhibit tumor growth in mouse models of cancer

FRIDAY, Nov. 18 (HealthDay News) -- The ortho- and meta-isoforms of tyrosine are associated with concomitant tumor resistance (CR), according to an experimental study published in the Nov. 15 issue of Cancer Research.

Raúl A. Ruggiero, Ph.D., from the Academia Nacional de Medicina in Buenos Aires, Argentina, and colleagues identified the serum factor associated with CR and described its origin, isolation, biological antitumor activity, and putative mechanism of tumor inhibition in BALB/c mice. The serum factor involved was identified using amino acid analysis and sequencing and mass spectrometry. Cell proliferation was measured using immunostaining. In vivo and in vitro experiments were used to investigate the molecular pathways underlying CR.

The investigators identified the serum factor as the meta- and ortho-isoforms of tyrosine. Both isoforms were found to inhibit tumor growth in three different murine models of cancer that generate CR. They also blocked metastasis in a fourth model that did not generate CR but was sensitive to tumor induced-CR. Early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of signal transducer and activator of transcription 3 were found to partially mediate antitumor effects of tyrosine isoforms.

"By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients," the authors write.

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