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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cells

Authors: Sahana Suresh Babu, Yanet Valdez, Andrea Xu, Alice M O’Byrne, Fernando Calvo, Victor Lei, Edward M Conway

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

CD248 is a cell surface glycoprotein, highly expressed by stromal cells and fibroblasts of tumors and inflammatory lesions, but virtually undetectable in healthy adult tissues. CD248 promotes tumorigenesis, while lack of CD248 in mice confers resistance to tumor growth. Mechanisms by which CD248 is downregulated are poorly understood, hindering the development of anti-cancer therapies.

Methods

We sought to characterize the molecular mechanisms by which CD248 is downregulated by surveying its expression in different cells in response to cytokines and growth factors.

Results

Only transforming growth factor (TGFβ) suppressed CD248 protein and mRNA levels in cultured fibroblasts and vascular smooth muscle cells in a concentration- and time-dependent manner. TGFβ transcriptionally downregulated CD248 by signaling through canonical Smad2/3-dependent pathways, but not via mitogen activated protein kinases p38 or ERK1/2. Notably, cancer associated fibroblasts (CAF) and cancer cells were resistant to TGFβ mediated suppression of CD248.

Conclusions

The findings indicate that decoupling of CD248 regulation by TGFβ may contribute to its tumor-promoting properties, and underline the importance of exploring the TGFβ-CD248 signaling pathway as a potential therapeutic target for early prevention of cancer and proliferative disorders.
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Metadata
Title
TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cells
Authors
Sahana Suresh Babu
Yanet Valdez
Andrea Xu
Alice M O’Byrne
Fernando Calvo
Victor Lei
Edward M Conway
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-113

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