scholarly journals Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

2006 ◽  
Vol 282 (7) ◽  
pp. 4924-4931 ◽  
Author(s):  
Maria V. Barbolina ◽  
Brian P. Adley ◽  
Edgardo V. Ariztia ◽  
Yueying Liu ◽  
M. Sharon Stack
Keyword(s):  
Matrix Metalloproteinase ◽  
Ovarian Carcinoma ◽  
Three Dimensional ◽  
Carcinoma Cells ◽  
Collagenolytic Activity ◽  
Type I ◽  
Collagen Gels ◽  
Ovarian Carcinoma Cells ◽  
Membrane Type

Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through the mesothelial cell layer and colonization of the submesothelial collagen-rich matrix. The objective of this study was to elucidate a potential mechanistic link between collagen adhesion and MT1-MMP expression. Our results indicate that culturing cells on three-dimensional collagen gels, but not thin layer collagen or synthetic threedimensional hydrogels, results in rapid induction of the transcription factor EGR1. Integrin signaling through a SRC kinase-dependent pathway is necessary for EGR1 induction. Silencing of EGR1 expression using small interfering RNA abrogated collagen-induced MT1-MMP expression and inhibited cellular invasion of three-dimensional collagen gels. These data support a model for intraperitoneal metastasis wherein collagen adhesion and clustering of collagen binding integrins activates integrin-mediated signaling via SRC kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed collagen invasion. This model highlights the role of unique interactions between ovarian carcinoma cells and interstitial collagens in the ovarian tumor microenvironment in inducing gene expression changes that potentiate intraperitoneal metastatic progression.

scholarly journals Expression of Membrane-Type 1, 2, and 3 Matrix Metalloproteinases Messenger RNA in Ovarian Carcinoma Cells in Serous Effusions

2001 ◽  
Vol 115 (4) ◽  
pp. 517-524 ◽  
Author(s):  
Ben Davidson ◽  
Iris Goldberg ◽  
Aasmund Berner ◽  
Jahn M. Nesland ◽  
Vered Givant-Horwitz ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Ovarian Carcinoma ◽  
Messenger Rna ◽  
Carcinoma Cells ◽  
Ovarian Carcinoma Cells ◽  
Membrane Type

scholarly journals Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis

2009 ◽  
Vol 20 (7) ◽  
pp. 2030-2040 ◽  
Author(s):  
Marc A. Lafleur ◽  
Daosong Xu ◽  
Martin E. Hemler
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Three Dimensional ◽  
Tumor Cell Invasion ◽  
Collagen Gels ◽  
Invasion And Metastasis ◽  
Lysosomal Degradation ◽  
Membrane Type ◽  
Pericellular Proteolysis

Membrane type-1 matrix metalloproteinase (MT1-MMP) supports tumor cell invasion through extracellular matrix barriers containing fibrin, collagen, fibronectin, and other proteins. Here, we show that simultaneous knockdown of two or three members of the tetraspanin family (CD9, CD81, and TSPAN12) markedly decreases MT1-MMP proteolytic functions in cancer cells. Affected functions include fibronectin proteolysis, invasion and growth in three-dimensional fibrin and collagen gels, and MMP-2 activation. Tetraspanin proteins (CD9, CD81, and TSPAN2) selectively coimmunoprecipitate and colocalize with MT1-MMP. Although tetraspanins do not affect the initial biosynthesis of MT1-MMP, they do protect the newly synthesized protein from lysosomal degradation and support its delivery to the cell surface. Interfering with MT1-MMP-tetraspanin collaboration may be a useful therapeutic approach to limit cancer cell invasion and metastasis.

scholarly journals Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Ubiquitination at Lys581Increases Cellular Invasion through Type I Collagen

2012 ◽  
Vol 287 (14) ◽  
pp. 11533-11545 ◽  
Author(s):  
Patricia A. Eisenach ◽  
Pedro Corrêa de Sampaio ◽  
Gillian Murphy ◽  
Christian Roghi
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Type I ◽  
Cellular Invasion ◽  
Membrane Type

scholarly journals Pancreatic Cancer Cells Respond to Type I Collagen by Inducing Snail Expression to Promote Membrane Type 1 Matrix Metalloproteinase-dependent Collagen Invasion

2011 ◽  
Vol 286 (12) ◽  
pp. 10495-10504 ◽  
Author(s):  
Mario A. Shields ◽  
Surabhi Dangi-Garimella ◽  
Seth B. Krantz ◽  
David J. Bentrem ◽  
Hidayatullah G. Munshi
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Type I Collagen ◽  
Epithelial Mesenchymal Transition ◽  
Three Dimensional ◽  
Type I ◽  
Collagen Gels ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Membrane Type

Pancreatic ductal adenocarcinoma (PDAC) is characterized by pronounced fibrotic reaction composed primarily of type I collagen. Although type I collagen functions as a barrier to invasion, pancreatic cancer cells have been shown to respond to type I collagen by becoming more motile and invasive. Because epithelial-mesenchymal transition is also associated with cancer invasion, we examined the extent to which collagen modulated the expression of Snail, a well known regulator of epithelial-mesenchymal transition. Relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels induced Snail. Inhibiting the activity or expression of the TGF-β type I receptor abrogated collagen-induced Snail. Downstream of the receptor, we showed that Smad3 and Smad4 were critical for the induction of Snail by collagen. In contrast, Smad2 or ERK1/2 was not involved in collagen-mediated Snail expression. Overexpression of Snail in PDAC cells resulted in a robust membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14)-dependent invasion through collagen-coated transwell chambers. Snail-expressing PDAC cells also demonstrated MT1-MMP-dependent scattering in three-dimensional collagen gels. Mechanistically, Snail increased the expression of MT1-MMP through activation of ERK-MAPK signaling, and inhibiting ERK signaling in Snail-expressing cells blocked two-dimensional collagen invasion and attenuated scattering in three-dimensional collagen. To provide in vivo support for our findings that Snail can regulate MT1-MMP, we examined the expression of Snail and MT1-MMP in human PDAC tumors and found a statistically significant positive correlation between MT1-MMP and Snail in these tumors. Overall, our data demonstrate that pancreatic cancer cells increase Snail on encountering collagen-rich milieu and suggest that the desmoplastic reaction actively contributes to PDAC progression.

scholarly journals Type I Collagen Abrogates the Clathrin-mediated Internalization of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) via the MT1-MMP Hemopexin Domain

2005 ◽  
Vol 281 (10) ◽  
pp. 6826-6840 ◽  
Author(s):  
Marc A. Lafleur ◽  
Francesca A. Mercuri ◽  
Neeracha Ruangpanit ◽  
Motoharu Seiki ◽  
Hiroshi Sato ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Type I ◽  
Membrane Type ◽  
Hemopexin Domain
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