TGFbeta and cancer metastasis: an inflammation link.

Dysregulated transforming growth factor beta (TGFbeta) signaling is observed in a variety of human cancers. TGFbeta is produced in large quantities by many tumor types and is known to be pro-oncogenic. Therapeutic strategies directed against TGFbeta signaling using neutralizing antibodies and small molecular inhibitors have been developed. However, TGFbeta is also found to function as a tumor suppressor. This switch from a tumor suppressor in premalignant stages of tumorigenesis to a tumor promoter in later stages of the disease poses great challenges in TGFbeta-targeted cancer therapy. It remains unclear what mechanisms underlie the dual role of TGFbeta and what factors mediate the switch. In the past, most work on dissecting underlying mechanisms was focused on differential regulation of signaling pathways by tumor cell autonomous TGFbeta signaling. Recent progress in elucidating TGFbeta effects on host immune/inflammatory reactions in the tumor microenvironment and distant organs brings exciting new perspectives to the field.