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、纤维连接蛋白和凝血酶原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。较小的整合素结合蛋白具有许多不同于结构支架的功能。一类小的整合素结合蛋白，由人类4号染色体上聚集的五个基因编码，被称为兄弟(小整合素结合配体，N-连锁糖蛋白)家族。成员包括骨涎蛋白、牙本质基质蛋白、牙本质涎磷蛋白、基质细胞外磷酸蛋白和骨桥蛋白。兄弟姐妹通常由骨骼组织表达，被认为在矿化以及细胞黏附和迁移中发挥作用。一些不同的癌症类型也会诱发特定的兄弟姐妹，包括乳腺癌、结肠癌、肺癌、胰腺癌、前列腺癌和甲状腺癌。个别兄弟姐妹家庭成员已被发现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家族的成员包含一个保守的胰岛素样生长因子(IGF)结合蛋白基序，是分泌的细胞外基质蛋白。CCNS参与多种生物学过程，如细胞黏附、迁移、增殖、分化和存活的调节。它们在妊娠、发育、血管生成、伤口修复和炎症中发挥重要作用。某些CCN基因似乎是肿瘤促进因子，而其他CCNS则表现出抑制能力。本次戈登研究会议的重点是定义最先进的关于小整合素结合蛋白在正常和病理状态下的生物学活动、生化相互作用和生理后果的知识。这项应用的具体目标是：(1)召集一个关于兄弟姐妹和CCN生物学的国际专家组；(2)通过多学科的陈述，确定小整合素结合蛋白在正常生理功能和癌症病理中的最新知识；(3)促进多个领域(生物化学、细胞生物学、分子生物学、肿瘤学、炎症、兄弟姐妹和CCN领域)的交叉受精；以及(4)激发翻译机会，开发将兄弟姐妹/CCNS用作病理状态标记并讨论治疗应用的新方法。这些目标与美国国立卫生研究院的使命直接相关。这种形式遵循戈登研究会议的标准模板，有一个晚上的介绍性会议，然后是4天的上午会议、下午晚些时候的海报会议和晚上的演讲，在一个促进科学前沿思想的公开、不受阻碍的讨论的环境中进行。将讨论的主要主题是：兄弟姐妹/CCNS的细胞内处理和功能；兄弟姐妹和CCN基因的遗传调控；兄弟姐妹和CCNS在癌症和炎症中的作用；以及兄弟姐妹/CCNS的生物活性片段。

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.