The Journal of Experimental Medicine
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 29 August 2005 doi:10.1084/jem.20042469
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 5, 617-624
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, S.
Right arrow Articles by Darling, T. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, S.
Right arrow Articles by Darling, T. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for tumor development

Shaowei Li1, Fumiko Takeuchi1, Ji-an Wang1, Christopher Fuller1, Gustavo Pacheco-Rodriguez2, Joel Moss2, and Thomas N. Darling1

1 Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
2 Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Thomas N. Darling: tdarling{at}usuhs.mil

Patients with tuberous sclerosis complex (TSC) develop hamartomatous tumors showing loss of function of the tumor suppressor TSC1 (hamartin) or TSC2 (tuberin) and increased angiogenesis, fibrosis, and abundant mononuclear phagocytes. To identify soluble factors with potential roles in TSC tumorigenesis, we screened TSC skin tumor–derived cells for altered gene and protein expression. Fibroblast-like cells from 10 angiofibromas and five periungual fibromas produced higher levels of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein than did fibroblasts from the same patient's normal skin. Conditioned medium from angiofibroma cells stimulated chemotaxis of a human monocytic cell line to a greater extent than conditioned medium from TSC fibroblasts, an effect blocked by neutralizing MCP-1–specific antibody. Overexpression of MCP-1 seems to be caused by loss of tuberin function because Eker rat embryonic fibroblasts null for Tsc2 (EEF Tsc2–/–) produced 28 times as much MCP-1 protein as did EEF Tsc2+/+ cells; transient expression of WT but not mutant human TSC2 by EEF Tsc2–/– cells inhibited MCP-1 production; and pharmacological inhibition of the Rheb-mTOR pathway, which is hyperactivated after loss of TSC2, decreased MCP-1 production by EEF Tsc2–/– cells. Together these findings suggest that MCP-1 is an important paracrine factor for TSC tumorigenesis and may be a new therapeutic target.

Abbreviations used: EEF, Eker rat embryonic fibroblast; IGFBP2, insulin-like growth factor-binding protein 2; LOH, loss of heterozygosity; MCP-1, monocyte chemoattractant protein-1; TSC, tuberous sclerosis complex; VEGF, vascular endothelial growth factor.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS