Characterization of a type IV collagen major cell binding site with affinity to the alpha 1 beta 1 and the alpha 2 beta 1 integrins.

Vandenberg, Philipp; Kern, Andreas; Ries, Albert; Luckenbill-Edds, Louise; Mann, Karlheinz; Kühn, Klaus

doi:10.1083/jcb.113.6.1475

Cited by 223 publications

(176 citation statements)

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“…The acquisition of a migratory/ metastatic phenotype is often associated with changes to the expression and activation states of integrins that affect cell attachment to ECM, regulate the balance between cell adhesion and motility and enable cell survival under conditions of detachment, a critical requirement for metastasis (reviewed in Felding-Habermann, 2003). The expression of a2b1 integrin, a type IV collagen receptor (Vandenberg et al, 1991), is regulated by growth factors and plays a role in angiogenesis (Senger et al, 1997), altered cell adhesion, survival, growth and metastasis of malignant cells (Krensel and Lichtner, 1999).…”

Section: Introductionmentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27 IGFÀIR murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen a1 and a2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/a2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by smallinterfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

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Section: Introductionmentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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“…Another characteristic feature of collagen IV is the presence of 21-26 interruptions in the collagenous Gly-Xaa-Yaa triple repeats. The interruptions in the collagenous domain not only provide molecular flexibility for network formation but some of them also serve as cell-binding sites and interchain crosslinking (Vandenberg et al, 1991). The number of interruptions varies between chains, being the lowest in the α1 chain with 21 interruptions and the highest in α4 chain with 26 interruptions (Table 1).…”

Section: Structural Properties and Supramolecular Organizationmentioning

confidence: 99%

“…A major binding site for α 1 β 1 and α 2 β 1 integrins has been originally identified within a triple-helical cyanogen bromide-derived fragment CB3, located 100 nm away from the amino-terminus of the collagen IV (Fig. 3) (Vandenberg et al, 1991). The triple-helical conformation of this particular region of the molecule is stabilized through interchain disulfide bridges between the α1(IV) and α2(IV) chains.…”

Section: Integrin Receptorsmentioning

confidence: 99%

Mammalian collagen IV

Khoshnoodi

Pedchenko

Hudson

2008

Microscopy Res & Technique

567

487

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Four decades have passed since the first discovery of collagen IV by Kefalides in 1966. Since then collagen IV has been investigated extensively by a large number of research laboratories around the world. Advances in molecular genetics have resulted in identification of six evolutionary related mammalian genes encoding six different polypeptide chains of collagen IV. The genes are differentially expressed during the embryonic development, providing different tissues with specific collagen IV networks each having unique biochemical properties. Newly translated α-chains interact and assemble in the endoplasmic reticulum in a chain-specific fashion and form unique heterotrimers. Unlike most collagens, type IV collagen is an exclusive member of the basement membranes and through a complex inter-and intramolecular interactions form supramolecular networks that influence cell adhesion, migration, and differentiation. Collagen IV is directly involved in a number of genetic and acquired disease such as Alport's and Goodpasture's syndromes. Recent discoveries have also highlighted a new and direct role for collagen IV in the development of rare genetic diseases such as cerebral hemorrhage and porencephaly in infants and hemorrhagic stroke in adults. Years of intensive investigations have resulted in a vast body of information about the structure, function, and biology of collagen IV. In this review article, we will summarize essential findings on the structural and functional relationships of different collagen IV chains and their roles in health and disease.

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“…Collagen V was further purified by chromatography on a Mono-Q column (18). Collagen IV tetramers that lack the globular NC1 domain were also isolated from a pepsin digest of human placenta (19). Previously described procedures were followed for the recombinant production, purification, and activation of matrix metalloproteinases (MMP) including collagenase-1 (MMP-1) (20), collagenase-3 (MMP-13) (21), gelatinase A (MMP-2) (22), gelatinase B (MMP-9) (23), stromelysin-1 (MMP-3), and matrilysin (MMP-7) (24).…”

Section: Sources Of Extracellular Matrix Ligands and Proteases-mentioning

confidence: 99%

Limited Cleavage of Extracellular Matrix Protein BM-40 by Matrix Metalloproteinases Increases Its Affinity for Collagens

Sasaki

Göhring

Mann

et al. 1997

Journal of Biological Chemistry

139

121

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The 33-kDa matrix protein BM-40 (SPARC, osteonectin) consists of an acidic N-terminal domain I, a central cysteine-rich follistatin-like module, and a C-terminal extracellular calcium-binding (EC) module. Previous studies attributed collagen IV and high affinity calcium binding of BM-40 to its EC module, which was shown by x-ray crystallography to consist of an EF-hand pair surrounded by several ␣-helical and loop segments. This module was now shown by surface plasmon resonance assay to bind with similar affinities to collagens I, III, and V. Cleavage of recombinant BM-40 and its EC module by collagenase-3, gelatinases A and B, matrilysin, and stromelysin-1 showed similar fragment patterns, whereas collagenase-1 was inactive. Some differences were, however, observed in cleavage rates and the preference of certain cleavage sites. Edman degradation of fragments demonstrated only three to four major cleavage sites in the central region of domain I and a single uniform cleavage in helix C of the EC module. Cleavage is accompanied by a 7-20-fold increase in binding activity for collagens I, IV, and V but revealed only small effects on calcium-dependent ␣-helical changes in the EC module. The data were interpreted to indicate that helix C cleavage is mainly responsible for enhancing collagen affinity by exposing the underlying helix A of the EC module. A similar activation may also occur in situ as indicated previously for tissue-derived BM-40.The small calcium-binding glycoprotein (33 kDa) referred to as BM-40, SPARC, or osteonectin has been shown to have a widespread occurrence in extracellular matrices of various organs with a particularly high expression found during morphogenesis, tissue remodeling, and repair. The protein exhibits anti-adhesive properties in cell culture and modulates the expression of certain extracellular receptors. Several extracellular ligands have been identified for BM-40 including some collagen types and cytokines (1). This indicated various binding sites on BM-40 in agreement with a previous proposal of a mosaic structure for the protein (2). The most recent interpretation of the domain structure based on recombinant deletion mutants and a crystal structure of a fragment encompassing the C-terminal 150 residues (3, 4) demonstrated an acidic and flexible N-terminal domain I (ϳ50 residues) followed by a follistatin-like (FS) 1 module (ϳ75 residues) and a novel extracellular calcium-binding (EC) module (ϳ150 residues). X-ray crystallography of this EC module demonstrated two opposing calcium-binding EF hands, as found in many intracellular proteins (5), which were in close contact to an extended ␣ helix (4). A combination of adjacent FS and EC modules has been detected in the cDNA sequences of several more extracellular proteins suggesting the existence of a protein family (1, 3, 4). Yet it is not known so far whether they are functionally related to BM-40.The binding of BM-40 to the fibril-forming collagens I, III, and V and basement membrane collagen IV has been demonstrated and depended ...

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Characterization of a type IV collagen major cell binding site with affinity to the alpha 1 beta 1 and the alpha 2 beta 1 integrins.

Cited by 223 publications

References 50 publications

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Mammalian collagen IV

Limited Cleavage of Extracellular Matrix Protein BM-40 by Matrix Metalloproteinases Increases Its Affinity for Collagens

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