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Y(1)-mediated effect of neuropeptide Y in cancer: breast carcinomas as targets

J C Reubi1, M Gugger, B Waser

  • 1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, CH-3010 Berne, Switzerland. reubi@patho.unibe.ch

Cancer Research
|June 5, 2001
PubMed

Insights

Neuropeptide Y (NPY) receptors, particularly the Y(1) subtype, are highly prevalent in breast cancer tissues, unlike normal breast tissue. This finding suggests NPY receptor targeting for novel breast cancer diagnostics and therapeutics.

Area of Science:

  • Oncology
  • Neuroendocrinology
  • Molecular Biology

Background:

  • Peptide receptors are clinically relevant targets in cancer diagnosis and therapy.
  • Neuropeptide Y (NPY) is a neurotransmitter involved in feeding and vasoconstriction, but its role in cancer was previously unknown.

Purpose of the Study:

  • To investigate the incidence and subtypes of Neuropeptide Y (NPY) receptors in human breast carcinomas.
  • To explore the functional role of NPY in breast cancer cell growth and its potential as a therapeutic target.

Main Methods:

  • In vitro receptor autoradiography was used to determine NPY receptor incidence in breast tumors and normal breast tissue.
  • In situ hybridization was employed to detect Y(1) and Y(2) messenger RNA (mRNA) in tumor and normal tissues, respectively.
  • Functional studies assessed the effect of NPY on SK-N-MC tumor cell growth.

Main Results:

  • A high incidence of NPY receptors was observed in 85% of primary breast carcinomas and 100% of lymph node metastases.
  • The Y(1) subtype predominated in breast carcinomas, while the Y(2) subtype was preferentially expressed in non-neoplastic breast tissue.
  • NPY induced a dose-dependent inhibition of tumor cell growth (>40%) in Y(1)-expressing cells, indicating a functional role.

Conclusions:

  • Neoplastic transformation of breast tissue is associated with a switch in NPY receptor expression from Y(2) to Y(1) subtype.
  • The high prevalence of Y(1) receptors in breast cancers suggests their potential as targets for NPY analogue-based diagnosis and therapy.
  • NPY should be considered a relevant small regulatory peptide in the context of cancer.

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