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

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

doi:10.1073/pnas.1830978100

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

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

Research output: Contribution to journal › Article › peer-review

333 Scopus citations

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 language	English (US)
Pages (from-to)	10954-10959
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	19
DOIs	https://doi.org/10.1073/pnas.1830978100
State	Published - Sep 16 2003
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1830978100

Cite this

Yin, J. J., Mohammad, K. S., Käkönen, S. M., Harris, S., Wu-Wong, J. R., Wessale, J. L., Padley, R. J., Garrett, I. R., Chirgwin, J. M., & Guise, T. A. (2003). A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proceedings of the National Academy of Sciences of the United States of America, 100(19), 10954-10959. https://doi.org/10.1073/pnas.1830978100

Yin, JJ, Mohammad, KS, Käkönen, SM, Harris, S, Wu-Wong, JR, Wessale, JL, Padley, RJ, Garrett, IR, Chirgwin, JM & Guise, TA 2003, 'A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 10954-10959. https://doi.org/10.1073/pnas.1830978100

@article{16ff8d78e2b340afb5a961d606f80e71,

title = "A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases",

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.",

author = "Yin, {Juan Juan} and Mohammad, {Khalid S.} and K{\"a}k{\"o}nen, {Sanna M.} and Stephen Harris and Wu-Wong, {J. Ruth} and Wessale, {Jerry L.} and Padley, {Robert J.} and Garrett, {I. Ross} and Chirgwin, {John M.} and Guise, {Theresa A.}",

year = "2003",

month = sep,

day = "16",

doi = "10.1073/pnas.1830978100",

language = "English (US)",

volume = "100",

pages = "10954--10959",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "19",

}

TY - JOUR

T1 - A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases

AU - Yin, Juan Juan

AU - Mohammad, Khalid S.

AU - Käkönen, Sanna M.

AU - Harris, Stephen

AU - Wu-Wong, J. Ruth

AU - Wessale, Jerry L.

AU - Padley, Robert J.

AU - Garrett, I. Ross

AU - Chirgwin, John M.

AU - Guise, Theresa A.

PY - 2003/9/16

Y1 - 2003/9/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0141479984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141479984&partnerID=8YFLogxK

U2 - 10.1073/pnas.1830978100

DO - 10.1073/pnas.1830978100

M3 - Article

C2 - 12941866

AN - SCOPUS:0141479984

SN - 0027-8424

VL - 100

SP - 10954

EP - 10959

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 19

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this