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PMID: 16826430 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bosentan inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis.

Clinical & experimental metastasis ·Vol. 23 ·No. 1 ·2006-00-00 ·Pages 41-53

Dréau D, Karaa A, Culberson C, Wyan H, McKillop IH, Clemens MG

Abstract

Angiogenic factors including endothelin-1 (ET-1) play a key role in the progression of breast metastases to bone. We investigated the impact of ET-1 on the development of bone metastases in an immunocompetent murine skin-fold chamber model. Murine mammary carcinoma 4T1 was injected in a skin-fold chamber implanted on CB6 mice along with bone explants. Furthermore, mice were treated with or without a dual selective antagonist of both ET-1 receptors. The progression of the vascularization within the chamber was monitored over time by intravital microscopy (IVM). The tumor growth and the development of bone metastases were assessed by cytokeratin-19 gene expression and histological studies. Results indicate that this new model associated with IVM allows for the continuous monitoring of the change in vascularization associated with the development of bone metastases. Additionally, treatment with an antagonist of both ET-1 receptors was associated with the presence of significantly less vessels near the tumor mass compared to control mice. These changes were correlated with smaller tumor masses and reduced bone invasion (P < 0.05). Thus, in an immunocompetent murine model of breast carcinoma metastases to bone, our data support the hypothesis that vascularization plays a role in tumor development and progression and that ET-1 specifically modulates the angiogenesis associated with breast metastases to the bone.

MeSH Terms
Angiogenesis Inhibitors/therapeutic use Animals Bone Neoplasms/blood supply,pathology,secondary Bosentan Breast Neoplasms/pathology Cell Division Endothelin-1/genetics Mammary Neoplasms, Animal/pathology Mice Mice, Inbred BALB C Mice, Inbred C57BL Models, Biological Neoplasm Metastasis/prevention & control RNA, Messenger/genetics Skin Sulfonamides/therapeutic use
Chemicals
Angiogenesis Inhibitors Endothelin-1 RNA, Messenger Sulfonamides Bosentan
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Dréau Didier
Department of Biology, University of North Carolina at Charlotte, Science & Technology Bldg, Rm. 490B, 9201 University City Blvd, Charlotte, NC 28223, USA. ddreau@email.uncc.edu
Karaa Amel
Culberson Cathy
Wyan Heather
McKillop Iain H
Clemens Mark G
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Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
DOI
10.1007/s10585-006-9016-z
Email
ddreau@email.uncc.edu
Published
2006-00-00
Epub
2006-00-07
Pages
41-53
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
External Links
PubMed source DOI: 10.1007/s10585-006-9016-z View journal details
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