Elevated SP/NK-1R in esophageal carcinoma promotes esophageal carcinoma cell proliferation and migration

Gene. 2015 Apr 15;560(2):205-10. doi: 10.1016/j.gene.2015.02.002. Epub 2015 Feb 7.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal malignant tumors, and currently there is no effective ways to manage the late stage disease. Therefore clarifying the mechanisms underlying the development of ESCC is of great importance to develop novel therapeutic agents. The present study focuses on the interaction between neurotransmitter substance P (SP) together with its receptor NK-1R and ESCC progression.

Methods: The distribution of SP positive nerve fibers and expression of NK-1R were detected in ESCC tissue using immunohistochemistry. The effects of SP stimulation and blocking on the growth and migration of ESCC cells were measured by in vitro and in vivo assay.

Results: A higher density of SP positive nerve fibers and elevated NK-1R expression on ESCC cells were observed. More importantly, the SP positive fiber density was correlated with tumor size and lymph node metastasis. SP promoted ESCC cell proliferation and migration by modulation of intracellular calcium levels.

Conclusion: NK-1R activation by SP stimulation promotes growth and migration of ESCC cells.

Keywords: Esophageal squamous cell carcinoma; Migration; NK-1R; Proliferation; Substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Imidazoles / pharmacology
  • Lymphatic Metastasis
  • Male
  • Mice, Nude
  • Middle Aged
  • Neurokinin-1 Receptor Antagonists / pharmacology
  • Piperidines / pharmacology
  • Receptors, Neurokinin-1 / metabolism*
  • Substance P / physiology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Calcium Channel Blockers
  • Imidazoles
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Receptors, Neurokinin-1
  • 3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
  • Substance P
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole