SD-208, a Novel Transforming Growth Factor β Receptor I Kinase Inhibitor, Inhibits Growth and Invasiveness and Enhances Immunogenicity of Murine and Human Glioma CellsIn vitroandIn vivo

Abstract

ABSTRACT

Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells

“…Studies with Smad3 knock-out mice demonstrated that these mice are resistant to chemical cutaneous carcinogenesis due to inhibition of keratinocyte proliferation and reduced skin inflammation (Li et al, 2004). In addition, a recent study provides evidence for the role of TGF-b signaling in promoting the growth and invasion of glioma cells (Uhl et al, 2004). Our results imply that Smad3 mediates the tumor-promoting activities of TGF-b on head and neck SCC cells by regulating the expression of potent matrix-degrading proteinases, MMP-13 and MMP-1, and thereby promoting the collagenolytic and invasive capacity of these malignant cells.…”

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…TGFb (Hjelmeland et al, 2004) and activin (Inman et al, 2002)) followed by reduced phosphorylation and nuclear translocation of Smads and diminished TGFbevoked protumorigenic cellular effects (Halder et al, 2005). Equally, SD-208 inhibits TGFb-mediated migration and invasion; however, viability and proliferation are not reduced in all the tumor cell models studied so far (Hayashi et al, 2004;Uhl et al, 2004). Additional small molecule inhibitors of TGFb-signaling such as SB-505124 (DaCosta Byfield et al, 2004) and A-83-01 (Tojo et al, 2005) have been shown to modulate TGF-familymember-mediated signaling, but the applicability of these substances for the treatment of HCC cells has not been shown so far.…”

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

“…SD208 is also a potent and selective inhibitor of TGF-␤RI. 30 Preparation and treatment with SD208 follows the previously mentioned procedure for SB431542.…”