Integrin α2β1 Is a Positive Regulator of Collagenase (MMP-1) and Collagen α1(I) Gene Expression

Riikonen, Terhi; Westermarck, Jukka; Koivisto, Leeni; Broberg, Arsi; Kähäri, Veli‐Matti; Heino, Jyrki

doi:10.1074/jbc.270.22.13548

Cited by 268 publications

(217 citation statements)

References 36 publications

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“…a3b1 integrin was shown to participate in phagocytosis of extracellular matrix (Coopman et al, 1996). a2b1, a3b1, a4b1, and a5b1 integrin were found to be involved in the regulation of matrix metalloprotease expression (Larjava et al, 1993;Huhtala et al, 1995;Riikonen et al, 1995). In addition, activation of a6b1 integrin increased invasiveness of LOX human melanoma cells correlating with a 2 ± 3-fold elevation of extracellular matrix degradation and invadopodial activity (Nakahra et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Third, integrins are necessary for basement membrane penetration, since RGD peptides interfering with ligand binding to certain integrins prevented this process in vitro (Gehlsen et al, 1988). And ®nally, integrins are involved in the regulation of protease expression and their localized activities, as demonstrated in tissue culture experiments (Huhtala et al, 1995;Riikonen et al, 1995;Brooks et al, 1996;Coopman et al, 1996;Nakahara et al, 1996). In vivo changes in the metastatic potential of tumor cells often correlated with changes of the integrin expression pattern.…”

Section: Introductionmentioning

confidence: 99%

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β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

Brakebusch

Wennerberg

Krell³

et al. 1999

Oncogene

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To investigate the role of b1 integrin during tumor metastasis, we established a ras-myc transformed ®broblastoid cell line with a disrupted b1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding b1A integrin resulted in b1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent b1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and b1 integrin expression. The metastasis potential of all three b1 integrin-expressing GERM 11 sublines tested was signi®cantly higher than that of the b1-de®cient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of ®bronectin, laminin-1, and collagen type I. b1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed ®broblasts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

Brakebusch

Wennerberg

Krell³

et al. 1999

Oncogene

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“…It was initially observed that antibodies blocking α 5 β 1 integrin-mediated adhesion induced MMP expression in fibroblasts (Werb et al, 1989). Later studies revealed that integrin-mediated signals are general regulators of MMP expression, as α 2 β 1 integrin regulates MMP-1 expression (Riikonen et al, 1995;Dumin et al, 2001), antibodies to α 3 β 1 integrin-tetraspanin complexes induce MMP-2 expression (Sugiura and Berditchevski, 1999), and α M β 2 and α 3 β 1 integrin ligation stimulates MMP-9 expression (Wize et al, 1998;Larjava et al, 1993). The effects on MMP expression are very specific.…”

Section: Expression and Secretion Of Gelatinases And Other Mmpsmentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

463

609

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“…Our previous data had shown Col 1 expression was two fold higher and expression for MMP-1, MMP-2, TIMP-1, and TIMP-2 increased for cells grown on 156 μg/cm 2 denatured collagen 17 . In this same study with 156 μg/cm 2 , with native collagen, Col-1 expression decreased by half and MMP-2 transcript levels increased by 2.5 fold in cell responses to denatured versus native collagen substrates at 4 day time points [35].…”

Section: Discussionmentioning

confidence: 82%

“…Cells recognize collagen matrices through the integrin family of transmembrane proteins; specifically, α 2 β 1 and α 1 β 1 integrin receptors [17]. The β1 integrins and the α2β1 integrin in particular have been associated with fibroblast collagen binding pathways [18,19].…”

Section: Introductionmentioning

confidence: 99%

Phagocytosis and remodeling of collagen matrices

Abraham

Dice

Lee

et al. 2007

Experimental Cell Research

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The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lung fibroblast behavior in vitro in terms of collagen uptake and matrix remodeling. Therefore, in the present work, the response of human fibroblasts (IMR-90) to the structural state of collagen was studied with respect to phagocytosis in the presence and absence of inhibitors. Protein content and transcript levels for Collagen I (Col-1), Matrix Metalloproteinase 1 (MMP-1), Matrix Metalloproteinase 2 (MMP-2), Tissue Inhibitor of Matrix Metalloproteinase 1 (TIMP-1), Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP-2), and Heat Shock Protein 70 (HSP-70) were characterized as a function of collagen matrix concentration, structure and cell culture time to assess effects on cellular collagen matrix remodeling processes. Phagocytosis of collagen was assessed quantitatively by uptake of collagen coated fluorescent beads incorporated into the pre-formed collagen matrices. Significantly higher levels of collagen phagocytosis were observed for the cells grown on the denatured collagen vs. native collagen matrices. Significant reduction in collagen phagocytosis was observed by blocking several phagocytosis pathways when the cells were grown on denatured collagen versus non-denatured collagen. Collagen phagocytosis inhibition effects were significantly greater for PDL57 IMR-90 cells versus PDL48 cells, reflecting a reduced number of collagen processing pathways available to the older cells. Transcript levels related to the deposition of new extracellular matrix proteins varied as a function of the structure of the collagen matrix presented to the cells. A four-fold increase in transcript level of Col-1 and a higher level of collagen matrix incorporation were observed for cells grown on denatured collagen versus cells grown on non-denatured collagen. The data suggest that biomaterial matrices incorporating denatured collagen may promote more active remodeling toward new extracellular matrices in comparison to cells grown on non-denatured collagen. A similar effect of cellular action toward denatured (wound-related) collagen in the remodeling of tissues in vivo may have significant impact on tissue regeneration as well as the progression of collagen-related diseases.

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Integrin α2β1 Is a Positive Regulator of Collagenase (MMP-1) and Collagen α1(I) Gene Expression

Cited by 268 publications

References 36 publications

β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

Gelatinase-mediated migration and invasion of cancer cells

Phagocytosis and remodeling of collagen matrices

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