? ? Large, integrin-binding proteins such as collagens, fibronectin, and thrombospondin are integral parts of established matrices and are generally discussed at other GRC meetings. Smaller integrin-binding proteins perform many functions other than those of structural scaffolding. One class of small, integrin-binding proteins encoded by five genes clustered on human chromosome 4 are called the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family. Members include bone sialoprotein, dentin matrix protein, dentin sialophosphoprotein, matrix extracellular phosphoglycoprotein, and osteopontin. Normally expressed by skeletal tissue, SIBLINGs are thought to play a role in mineralization as well as cellular adhesion and migration. Specific SIBLINGs are also induced in a number of different cancer types including breast, colon, lung, pancreatic, prostate, and thyroid cancers. Individual SIBLING family members have been found to promote angiogenesis and invasiveness. A second small integrinbinding gene family is the connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family of proteins. Members of the CNN family contain a conserved insulin-like growth factor (IGF) binding protein motif and are secreted extracellular matrix proteins. CCNs are involved in diverse biological processes such as regulation of cell adhesion, migration, proliferation, differentiation and survival. They play important roles in pregnancy, development, angiogenesis, wound repair and inflammation. Certain CCN genes appear to act as tumor-promoting factors, while other CCNs exhibits suppressive capabilities. The focus of this Gordon Research Conference is on defining state-of-the-art knowledge of the biological activities, biochemical interactions and physiological consequences of small-integrin binding proteins in normal and pathological states. This application has as its specific aims to: (1) Convene an international group of experts on SIBLING and CCN biology; (2) Through multidisciplinary presentations determine the state of the art knowledge on small integrin binding proteins in normal physiological function and cancer pathology; (3) Facilitate cross-fertilization of multiple fields (biochemistry, cell biology, molecular biology, oncology, inflammation, the SIBLING and CCN fields); and (4) spark translational opportunities in the development of novel ways to use SIBLINGs/CCNs as markers for pathological states and discuss therapeutic applications.
These aims are directly relevant to the mission of the NIH. The format follows the standard template for a Gordon Research Conference, with an evening introductory evening session, followed by 4 days of morning sessions, late afternoon poster sessions and evening talks in an environment facilitating the open, unhampered discussion of ideas at the frontiers of science. The principal topics to be addressed are: intracellular processing and function of SIBLINGs/CCNs; genetic regulation of SIBLING and CCN genes; SIBLINGs and CCNs in cancer and inflammation; and bioactive fragments of SIBLINGs/CCNs. ? ? ? ?
