According to study author, Dr. Marcus F. Neurath from the University of Mainz in Germany, "Several lines of evidence support an important role of TGF-b in the development of colorectal cancer. For instance, mutations of the TGF-b receptor II are frequently observed in patients with colon cancer suggesting a potential role for TGF-b in preventing colon carcinogenesis." However, the molecular mechanisms that control colon cancer are poorly understood. Dr. Neurath and colleagues used a mouse model of colon cancer to show that carcinogenesis in the colon is highly dependent on TGF-b production in tumor infiltrating T lymphocytes. Specifically, a form of the cytokine interleukin (IL)-6 was shown to play a key role and inhibition of TGF-b-dependent IL-6 trans-signaling prevented tumor progression.
The researchers conclude that development and progression of colorectal cancer is dependent on TGF-b production in tumor infiltrating T lymphocytes via a TGF-b –dependent mechanism controlling IL-6 trans-signaling. "Taken together, our data provide novel insights into TGF-b signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-b-dependent IL-6 trans-signaling," explains Dr. Neurath.
Christoph Becker, Massimo C. Fantini, Christoph Schramm, Hans A. Lehr, Stefan Wirtz, Alexei Nikolaev, Jürgen Burg, Susanne Strand, Ralf Kiesslich, Samuel Huber, Hiroaki Ito, Norihiro Nishimoto, Kazuyuki Yoshizaki, Tadamitsu Kishimoto, Peter R. Galle, Manfred Blessing, Stefan Rose-John, and Markus F. Neurath: "TGF-Beta Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling"
Publishing in Immunity, Volume 21, Number 4, pages 491–501.
Journal
Immunity