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Y₁-Mediated Effect of Neuropeptide Y in Cancer

Breast Carcinomas as Targets

Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland

Overexpression of selected peptide receptors in human tumors has been shown to represent clinically relevant targets for cancer diagnosis and therapy. Neuropeptide Y (NPY) is a peptide neurotransmitter mediating feeding behavior and vasoconstriction. It has never been shown to be involved in human cancer. We show here, using in vitro receptor autoradiography, a NPY receptor incidence of 85% in primary human breast carcinomas (n = 95) and of 100% in lymph node metastases of receptor-positive primaries (n = 27), predominantly as Y₁ subtype, whereas non-neoplastic human breast expressed Y₂ preferentially. Y₁ mRNA was detected in Y₁-expressing tumors by in situ hybridization, whereas Y₂ mRNA was found in normal breast tissue. The strong predominance of Y₁ in breast carcinomas compared with Y₂ in normal breast suggests that neoplastic transformation can switch the NPY receptor expression from Y₂ to Y₁ subtype. Moreover, in Y₁-expressing human SK-N-MC tumor cells, an NPY-induced, dose-dependent inhibition of tumor cell growth of >40% was observed, suggesting a functional role of NPY in cancer, mediated by Y₁. NPY should therefore be added to the list of small regulatory peptides related to cancer. The high incidence of Y₁ in in situ, invasive, and metastatic breast cancers allows for the possibility to target them for diagnosis and therapy with NPY analogues.

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