TGF-β Signaling and Biglycan in Pancreatic Cancer

Abstract

The small leucine-rich proteoglycan (SLRP) biglycan is a major constituent of many extracellular matrices and is overexpressed in stroma-rich tumors such as pancreatic carcinoma. Here, biglycan is produced by both stromal cells and tumor cells and through its ability to act as a binding protein for TGF-β and other growth factors, and to directly inhibit proliferation of tumor cells, this SLRP is involved in various aspects of tumor biology. Biglycan expression itself is controlled by TGF-β and represents an established marker of TGF-β activity. The focus of our work during the past years has been to elucidate the molecular mechanisms and signaling pathways involved in TGF-β regulation of biglycan using pancreatic tumor cells as the principal cellular model. In this chapter, we review some of the most significant observations published previously and, in addition, present data on the role of intracellular mediators which have not been implicated in TGF-β control of biglycan so far. Besides providing a basis for pharmacologic interference with TGF-β-induced fibrotic tissue formation through specific inhibition of biglycan. TGF-β regulation of biglycan represents a paradigm of how specificity and complexity in TGF-β signaling is achieved at both the cellular and gene level.