The roles of substrate thermal stability and P2 and P1' subsite identity on matrix metalloproteinase triple-helical peptidase activity and collagen specificity.
AuthorsMinond D, Lauer-Fields JL, Cudic M, Overall CM, Pei D, Brew K, Visse R, Nagase H, Fields GB
JournalJ Biol Chem
PubMed ID17065155
'The hydrolysis of collagen (collagenolysis) is one of the committed steps in extracellular matrix turnover. Within the matrix metalloproteinase (MMP) family distinct preferences for collagen types are seen. The substrate determinants that may guide these specificities are unknown. In this study, we have utilized 12 triple-helical substrates in combination with ... More
Type I collagen contains at least 14 cryptic fibronectin binding sites of similar affinity.
AuthorsIngham KC, Brew SA, Migliorini M
JournalArch Biochem Biophys
PubMed ID12413494
'There is uncertainty in the literature regarding the number and location of fibronectin binding sites on denatured collagen. Although most attention has focused on a single site near the collagenase-sensitive region of each alpha chain, there is evidence for additional sites in other regions. We treated bovine type I collagen ... More
TGF-beta1 + EGF-initiated invasive potential in transformed human keratinocytes is coupled to a plasmin/MMP-10/MMP-1-dependent collagen remodeling axis: role for PAI-1.
AuthorsWilkins-Port CE, Ye Q, Mazurkiewicz JE, Higgins PJ,
JournalCancer Res
PubMed ID19383899
'The phenotypic switching called epithelial-to-mesenchymal transition is frequently associated with epithelial tumor cell progression from a comparatively benign to an aggressive, invasive malignancy. Coincident with the emergence of such cellular plasticity is an altered response to transforming growth factor-beta (TGF-beta) as well as epidermal growth factor (EGF) receptor amplification. TGF-beta ... More
Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype.
AuthorsIssa A, Le TX, Shoushtari AN, Shields JD, Swartz MA,
JournalCancer Res
PubMed ID19118020
'Most carcinomas spread to distant sites through lymphatic vessels. Several preclinical and clinical studies have shown a positive correlation between the incidence of lymph node metastasis and secretion of the lymphatic growth factor vascular endothelial growth factor-C (VEGF-C) by tumor cells, suggesting tumor lymphangiogenesis as an escape mechanism. However, recent ... More
Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases: review and protocols.
AuthorsFrederiks WM, Mook OR
JournalJ Histochem Cytochem
PubMed ID15150280
'Proteases are essential for protein catabolism, regulation of a wide range of biological processes, and in the pathogenesis of many diseases. Several techniques are available to localize activity of proteases in tissue sections or cell preparations. For localization of the activity of matrix metalloproteinases, in situ zymography was introduced some ... More
Functional imaging of tumor proteolysis.
AuthorsSloane BF, Sameni M, Podgorski I, Cavallo-Medved D, Moin K
JournalAnnu Rev Pharmacol Toxicol
PubMed ID16402907
'The roles of proteases in cancer are now known to be much broader than simply degradation of extracellular matrix during tumor invasion and metastasis. Furthermore, proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, endothelial cells) as well as tumor cells are recognized to contribute to pathways critical to neoplastic progression. ... More
Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells.
AuthorsGoda S, Inoue H, Umehara H, Miyaji M, Nagano Y, Harakawa N, Imai H, Lee P, Macarthy JB, Ikeo T, Domae N, Shimizu Y, Iida J,
JournalAm J Pathol
PubMed ID16877347
Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood. In this study, we show that CXCL12 significantly enhanced ... More
Imaging and quantifying the dynamics of tumor-associated proteolysis.
The roles of proteases in cancer are dynamic. Furthermore, the roles or functions of any one protease may differ from one stage of cancer to another. Proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, endothelial cells) as well as from tumor cells make important contributions to 'tumor proteolysis'. Many tumors ... More
NMR and bioinformatics discovery of exosites that tune metalloelastase specificity for solubilized elastin and collagen triple helices.
The catalytic domain of metalloelastase (matrix metalloproteinase-12 or MMP-12) is unique among MMPs in exerting high proteolytic activity upon fibrils that resist hydrolysis, especially elastin from lungs afflicted with chronic obstructive pulmonary disease or arteries with aneurysms. How does the MMP-12 catalytic domain achieve this specificity? NMR interface mapping suggests ... More
Mesenchymal cells stimulate capillary morphogenesis via distinct proteolytic mechanisms.
AuthorsGhajar CM, Kachgal S, Kniazeva E, Mori H, Costes SV, George SC, Putnam AJ,
JournalExp Cell Res
PubMed ID20067788
During angiogenesis, endothelial cells (ECs) degrade their surrounding extracellular matrix (ECM) to facilitate invasion. How interactions between ECs and other cells within their microenvironment facilitate this process is only partially understood. We have utilized a tractable 3D co-culture model to investigate the proteolytic mechanisms by which pre-committed or more highly ... More
In vivo evidence for active matrix metalloproteinases in human endometrium supports their role in tissue breakdown at menstruation.
AuthorsZhang J, Salamonsen LA
JournalJ Clin Endocrinol Metab
PubMed ID11994386
Human endometrium remodels extensively during each reproductive cycle culminating in loss of most functionalis tissue at menstruation. Evidence suggests that menstruation results from the action of the matrix metalloproteinases (MMP), enzymes secreted in latent forms. MMP activation is thus an important regulatory step. It has not been established that MMPs ... More
Hyperoxia-induced emphysematous changes in subacute phase of endotoxin-induced lung injury in rats.
AuthorsKohno M, Ishizaka A, Sawafuji M, Koh H, Hirayama Y, Ikeda E, Shiomi T, Ohashi A, Okada Y, Kobayashi K
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID15003927
We examined the effects of prolonged hyperoxia (75% O(2)) on lung structure and collagen metabolism in the subacute phase of lung injury induced by continuous infusion of endotoxin (LPS) in a rat model. Experimental groups included control, endotoxin alone, endotoxin plus hyperoxia, and hyperoxia alone. Endotoxin-treated rats received a bolus ... More
SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.