A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases

Juan Juan Yin, Khalid Mohammad, Sanna M. Käkönen, Stephen Harris, J. Ruth Wu-Wong, Jerry L. Wessale, Robert J. Padley, I. Ross Garrett, John Chirgwin, Theresa Guise

Research output: Contribution to journalArticle

284 Citations (Scopus)

Abstract

Osteoblastic bone metastases are common in prostate and breast cancer patients, but mechanisms by which tumor cells stimulate new bone formation are unclear. We identified three breast cancer cell lines that cause osteoblastic metastases in a mouse model and secrete endothelin-1. Tumor-produced endothelin-1 stimulates new bone formation in vitro and osteoblastic metastases in vivo via the endothelin A receptor. Treatment with an orally active endothelin A receptor antagonist dramatically decreased bone metastases and tumor burden in mice inoculated with ZR-75-1 cells. Tumor-produced endothelin-1 may have a major role in the establishment of osteoblastic bone metastases, and endothelin A receptor blockade represents effective treatment.

Original languageEnglish (US)
Pages (from-to)10954-10959
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number19
DOIs
StatePublished - Sep 16 2003
Externally publishedYes

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Endothelin-1
Neoplasm Metastasis
Bone and Bones
Endothelin A Receptors
Osteogenesis
Breast Neoplasms
Neoplasms
Tumor Burden
Prostatic Neoplasms
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. / Yin, Juan Juan; Mohammad, Khalid; Käkönen, Sanna M.; Harris, Stephen; Wu-Wong, J. Ruth; Wessale, Jerry L.; Padley, Robert J.; Garrett, I. Ross; Chirgwin, John; Guise, Theresa.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 19, 16.09.2003, p. 10954-10959.

Research output: Contribution to journalArticle

Yin, Juan Juan ; Mohammad, Khalid ; Käkönen, Sanna M. ; Harris, Stephen ; Wu-Wong, J. Ruth ; Wessale, Jerry L. ; Padley, Robert J. ; Garrett, I. Ross ; Chirgwin, John ; Guise, Theresa. / A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 19. pp. 10954-10959.
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