2007 Small Intergin Binding Proteins Gordon Research Conference

描述（由申请人提供）： 大的整合素结合蛋白，如胶原蛋白、纤连蛋白和血小板反应蛋白是已建立的基质的组成部分，通常在其他GRC会议上讨论。较小的整联蛋白结合蛋白执行许多功能以外的结构支架。一类由聚集在人类4号染色体上的5个基因编码的小的整合素结合蛋白被称为SIBLING（小整合素结合配体，N-连接糖蛋白）家族。成员包括骨唾液蛋白、牙本质基质蛋白、牙本质唾液磷蛋白、基质细胞外磷酸糖蛋白和骨桥蛋白。通常由骨骼组织表达，SIBLING被认为在矿化以及细胞粘附和迁移中起作用。特异性SIBLING也在许多不同的癌症类型中被诱导，包括乳腺癌、结肠癌、肺癌、胰腺癌、前列腺癌和甲状腺癌。已发现个别SIBLING家族成员促进血管生成和侵袭性。第二个小整合素结合基因家族是结缔组织生长因子/富含半胱氨酸的61/肾母细胞瘤过表达（CCN）蛋白家族。CNN家族的成员含有保守的胰岛素样生长因子（IGF）结合蛋白基序，并且是分泌的细胞外基质蛋白。CCN参与多种生物学过程，例如调节细胞粘附、迁移、增殖、分化和存活。它们在妊娠、发育、血管生成、伤口修复和炎症中起重要作用。某些CCN基因似乎起肿瘤促进因子的作用，而其他CCN则表现出抑制能力。这次戈登研究会议的重点是定义最先进的知识的生物活性，生化相互作用和生理后果的小整合素结合蛋白在正常和病理状态。本申请的具体目的是：（1）召集SIBLING和CCN生物学方面的国际专家组;（2）通过多学科的介绍，确定关于正常生理功能和癌症病理学中的小整联蛋白结合蛋白的最新知识;（3）促进多领域交叉发展（生物化学、细胞生物学、分子生物学、肿瘤学、炎症、SIBLING和CCN领域）;和（4）在开发使用SIBLING/CCN作为病理状态的标志物，并讨论治疗应用。这些目标与NIH的使命直接相关。该格式遵循戈登研究会议的标准模板，晚上的介绍性晚间会议，随后是4天的上午会议，下午晚些时候的海报会议和晚上的会谈，在一个环境中促进开放，不受阻碍地讨论科学前沿的想法。要解决的主要问题是：胞内加工和功能的SIBLING/CCN;遗传调控的SIBLING和CCN基因; SIBLING和CCN在癌症和炎症;和生物活性片段的SIBLING/CCN。

DESCRIPTION (provided by applicant): 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.