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Fibulin-5, an integrin-binding matricellular protein: its function in development and disease.

ABSTRACT: Interactions between the extracellular matrix (ECM) and cells are critical in embryonic development, tissue homeostasis, physiological remodeling, and tumorigenesis. Matricellular proteins, a group of ECM components, mediate cell-ECM interactions. One such molecule, Fibulin-5 is a 66-kDa glycoprotein secreted by various cell types, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. Fibulin-5 contributes to the formation of elastic fibers by binding to structural components including tropoelastin and fibrillin-1, and to cross-linking enzymes, aiding elastic fiber assembly. Mice deficient in the fibulin-5 gene (Fbln5) exhibit systemic elastic fiber defects with manifestations of loose skin, tortuous aorta, emphysematous lung and genital prolapse. Although Fbln5 expression is down-regulated after birth, following the completion of elastic fiber formation, expression is reactivated upon tissue injury, affecting diverse cellular functions independent of its elastogenic function. Fibulin-5 contains an evolutionally conserved arginine-glycine-aspartic acid (RGD) motif in the N-terminal region, which mediates binding to a subset of integrins, including alpha5beta1, alphavbeta3, and alphavbeta5. Fibulin-5 enhances substrate attachment of endothelial cells, while inhibiting migration and proliferation in a cell type- and context-dependent manner. The antagonistic function of fibulin-5 in angiogenesis has been demonstrated in vitro and in vivo; fibulin-5 may block angiogenesis by inducing the anti-angiogenic molecule thrompospondin-1, by antagonizing VEGF(165)-mediated signaling, and/or by antagonizing fibronectin-mediated signaling through directly binding and blocking the alpha5beta1 fibronectin receptor. The overall effect of fibulin-5 on tumor growth depends on the balance between the inhibitory property of fibulin-5 on angiogenesis and the direct effect of fibulin-5 on proliferation and migration of tumor cells. However, the effect of tumor-derived versus host microenvironment-derived fibulin-5 remains to be evaluated.

SUBMITTER: Yanagisawa H

PROVIDER: S-EPMC2778585 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Fibulin-5, an integrin-binding matricellular protein: its function in development and disease.

Yanagisawa Hiromi H Schluterman Marie K MK Brekken Rolf A RA

Journal of cell communication and signaling 20091002 3-4

Interactions between the extracellular matrix (ECM) and cells are critical in embryonic development, tissue homeostasis, physiological remodeling, and tumorigenesis. Matricellular proteins, a group of ECM components, mediate cell-ECM interactions. One such molecule, Fibulin-5 is a 66-kDa glycoprotein secreted by various cell types, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. Fibulin-5 contributes to the formation of elastic fibers by binding to structural c ...[more]

PMID: 19798595

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Project description:Tumor microenvironment is considered nowadays as one of the main players in cancer development and progression. Tumor microenvironment is highly complex and consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial cells, or infiltrating leukocytes) and a large list of extracellular matrix proteins and soluble factors. The way that microenvironment components interact among them and with the tumor cells is very complex and only partially understood. However, it is now clear that these interactions govern and modulate many of the cancer hallmarks such as cell proliferation, the resistance to death, the differentiation state of tumor cells, their ability to migrate and metastasize, and the immune response against tumor cells. One of the microenvironment components that have emerged in the last years with strength is a heterogeneous group of multifaceted proteins grouped under the name of matricellular proteins. Matricellular proteins are a family of non-structural matrix proteins that regulate a variety of biological processes in normal and pathological situations. Many components of this family such as periostin (POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to regulate key aspect of tumor biology, including proliferation, invasion, matrix remodeling, and dissemination to pre-metastatic niches in distant organs. Matricellular proteins can be produced by tumor cells themselves or by tumor-associated cells, and their synthesis can be affected by intrinsic and/or extrinsic tumor cell factors. In this review, we will focus on the role of POSTN in the development and progression of cancer. We will describe their functions in normal tissues and the mechanisms involved in their regulation. We will analyze the tumors in which their expression is altered and their usefulness as a biomarker of tumor progression. Finally, we will speculate about future directions for research and therapeutic approaches targeting POSTN.

Dataset Information

Fibulin-5, an integrin-binding matricellular protein: its function in development and disease.

Publications

Fibulin-5, an integrin-binding matricellular protein: its function in development and disease.

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