Open Access Research article

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

Sahana Suresh Babu1, Yanet Valdez1, Andrea Xu1, Alice M O’Byrne1, Fernando Calvo23, Victor Lei1 and Edward M Conway1*

Author Affiliations

1 Centre for Blood Research, Department of Medicine, University of British Columbia, 4306-2350 Health Sciences Mall, V6T 1Z3, BC Vancouver, Canada

2 Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK

3 Tumour Microenvironment Team Division of Cancer Biology, The Institute of Cancer Research, London, UK

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BMC Cancer 2014, 14:113  doi:10.1186/1471-2407-14-113

Published: 20 February 2014



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.


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.


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.


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.