Background:

CD248 is a type-I transmembrane glycoprotein that is expressed by mesenchymal cells during fetal development, but is absent in most normal adult tissues. In response to inflammation and cancer, CD248 is markedly upregulated. Mice lacking CD248 are resistant to tumor development and inflammatory stimuli. Moreover, CD248 has been shown to be important in cytokine-induced cell migration. Means to suppress expression of CD248 may therefore be of therapeutic value. However, the mechanisms by which CD248 is suppressed are not understood.

Aim:

We aimed to assess whether the tumor suppressor, TGF-β, could modulate expression and function of CD248.

Results:

By Western immunoblotting, flow cytometry and immunofluorescence studies, we determined that TGFβ suppresses expression of CD248 in cultured primary murine embryonic fibroblasts (MEFs) and neonatal aortic smooth muscle cells. Real time RT-PCR studies revealed that TGF-β down-regulates CD248 gene transcription. TGF-β-induced suppression of CD248 was depedent on activation of Activin like kinase-5 (ALK-5), a receptor for TGF-β, and correlated with phosphorylation of SMAD-2. We tested the migratory response of MEFs to PDGF-β with and without TGF-β. MEFs lacking CD248 (derived from CD248 knockout mice) did not migrate, whereas wild-type MEFs readily migrated in response to PDGF-β. However, the addition of TGF-β to the PDGF-β almost totally suppressed migration of the wild-type MEFs, to a similar extent as seen with the CD248-knockout MEFs.

Conclusion:

Our novel findings that TGF-β suppresses CD248 expression and function supports the notion that this and related intracellular pathways might be targeted to reduce the cellular events that promote inflammation and/or cancer.