help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2008.070732 on June 5, 2008

Published online before print June 5, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ajpath.2008.070732v1
173/1/253    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van Deventer, H. W.
Right arrow Articles by Serody, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Deventer, H. W.
Right arrow Articles by Serody, J. S.
(American Journal of Pathology. 2008;173:253-264.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070732

C-C Chemokine Receptor 5 on Pulmonary Fibrocytes Facilitates Migration and Promotes Metastasis via Matrix Metalloproteinase 9

Hendrik W. van Deventer*{dagger}, Qing Ping Wu{dagger}, Daniel T. Bergstralh{ddagger}, Beckley K. Davis{ddagger}, Brian P. O'Connor{ddagger}, Jenny P.-Y. Ting{dagger}{ddagger} and Jonathan S. Serody*{dagger}{ddagger}

From the Department of Medicine,* Division of Hematology/Oncology, the Department of Microbiology and Immunology,{ddagger} and the Lineberger Comprehensive Cancer Center,{dagger} University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Previously, our group has used a B16-F10 melanoma model to show that C-C chemokine receptor 5 (CCR5) knockout (CCR5–/–) mice form fewer pulmonary metastases than wild-type mice. This advantage can be eliminated by injecting CCR5–/– mice with wild-type pulmonary mesenchymal cells before tumor injection. In this article, we present the mechanisms underlying this finding. First, we demonstrate that wild-type mesenchymal cells migrate to CCL4 more efficiently in vitro than CCR5–/– cells. Wild-type mesenchymal cells were also 3.6 (1.85 to 5.85) times more efficient than CCR5–/– cells at migrating into the lung after intravenous injection (P < 0.01). The injection of wild-type but not CCR5–/– mesenchymal cells led to a 7.0 ± 1.6 (P < 0.05)-fold induction of matrix metalloproteinase 9 (MMP9) in the host lung. Neither wild-type nor CCR5–/– cells caused significant increases in MMP2, MMP3, or MMP8. Inhibition of the gelatinase activity of MMP9 decreased the number of metastases and restored the advantage that CCR5–/– mice have over wild-type mice. Further analysis showed that the CCR5+ mesenchymal cells expressed CD45+ and CD13+ but did not express {alpha}-smooth muscle actin. This phenotype is characteristic of a subset of mesenchymal cells called fibrocytes. Together, these data suggest a novel role for CCR5 in the migration of pulmonary fibrocytes and the promotion of metastasis.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. Barroso-Gonzalez, N. El Jaber-Vazdekis, L. Garcia-Exposito, J.-D. Machado, R. Zarate, A. G. Ravelo, A. Estevez-Braun, and A. Valenzuela-Fernandez
The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities
J. Biol. Chem., June 12, 2009; 284(24): 16609 - 16620.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. B. Moore
Fibrocytes as Potential Biomarkers in Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 524 - 525.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American Society for Investigative Pathology.