The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential

Tammy A. Castro, Marion C. Cohen, Pranela Rameshwar

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Breast cancer has a predilection for metastasis to the bone marrow. The preprotachykinin-I (PPT-I) gene has a central role in the early migration of breast cancer cells into the bone marrow, making this organ a latent repository of the cancer cells. This study investigated whether the invasive and metastatic potential of breast cancer cells correlate with the expression of the PPT-I gene and the receptors for its peptides, neurokinin-1 (NK-1) and NK-2. The studies compared cells that are non-tumorigenic (MCF12A), low metastatic and invasive potential (MCF7), and sublines of MCF with increased invasive and metastatic potential (LCC1 and LCC2). LCC2, but not LCC1 is tamoxifen resistant. Quantitative RT-PCR showed increased expression of PPT-I, NK-1 and NK-2 mRNA LCC1 and LCC2. MCF7 required stimulation by phorbol ester for NK-1 induction. The levels of NK-2 mRNA were significantly increased in LCC2. Clonogenic assays with specific receptor antagonists showed a predominant role for NK-2 in the proliferation of both LCC1 and LCC2. While the growth rate of LCC1 and LCC2 were similar, the latter showed increased migration. Use of a nude mouse model confirmed higher metastatic potential of LCC2, including increased migration to regions of the endosteum. Overall, these studies show a correlation between three neuroendocrine-related genes: PPT-I, NK-1 and NK-2 and the metastatic potential of specific breast cancer cells. These cells provide a model for future studies on bone marrow metastasis.

Original languageEnglish (US)
Pages (from-to)621-628
Number of pages8
JournalClinical and Experimental Metastasis
Volume22
Issue number8
DOIs
StatePublished - Dec 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Bone marrow metastasis
  • Breast cancer
  • Early metastasis
  • Neurokinin-1
  • Preprotachykinin-1
  • Substance P

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