Endothelin-3 is produced by metastatic melanoma cells and promotes melanoma cell survival

J Cutan Med Surg. 2008 Mar-Apr;12(2):64-70. doi: 10.2310/7750.2008.06164.

Abstract

Background: Endothelin-3 (ET-3) is an essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development. Its expression is tightly regulated, being completely turned off in adult skin.

Objective: In this study, results are presented that demonstrate abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies and cell culture. Further, in vitro experiments showed that metastatic melanoma cells have the capacity to respond to ET-3 stimulation by increasing survival.

Conclusion: Therefore, an abnormal autocrine stimulation pathway involving ET-3 is present in metastatic melanoma cells. Blocking this signal transduction pathway may prove useful for the treatment of metastatic melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Survival / physiology
  • Endothelin-3 / biosynthesis*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Melanocytes
  • Melanoma / metabolism*
  • Melanoma / secondary
  • Nevus / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / secondary
  • Tumor Cells, Cultured

Substances

  • Endothelin-3
  • RNA, Messenger