Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral squamous cell carcinoma (SCC) is characterized by invasive growth and the propensity for distant metastasis. The expression of specific adhesion receptors promotes defined interactions with the specific components found within the extracellular matrix (ECM). We previously showed that the alpha v beta 6 fibronectin receptor is highly expressed in oral SCC. Here we forced expression of the beta 6 subunit into poorly invasive SCC9 cells to establish the SCC9 beta 6 cell line and compared these two cell lines in several independent assays. Whereas adhesion to fibronectin was unaffected by the expression of beta 6, migration on fibronectin and invasion through a reconstituted basement membrane (RBM) were both increased. Function-blocking antibodies to alpha v beta 6 (10D5) reduced both migration on fibronectin and invasion through an RBM, whereas anti-alpha 5 antibodies were effective only in suppressing migration on fibronectin, not invasion. Expression of beta 6 also promoted tumor growth and invasion in vivo and modulated fibronectin matrix deposition. When grown as a co-culture with SCC9 cells, peritumor fibroblasts (PTF) organized a dense fibronectin matrix. However, fibronectin matrix assembly was decreased in co-cultures of SCC9 beta 6 cells and PTF and this decrease was reversed by the addition of function-blocking anti-alpha v beta 6 antibodies. The expression of beta 6 also resulted in increased levels of matrix metalloproteinase 3. Addition of the general MMP inhibitor GM6001 to SCC9 beta 6/PTF co-cultures dramatically increased fibronectin matrix assembly in a similar fashion as incubation with anti-alpha v beta 6 antibodies. These results demonstrate that expression of beta 6 (1) increases oral SCC cell motility and growth in vitro and in vivo; (2) negatively affects fibronectin matrix assembly; and (3) stimulates the expression and activation of MMP3. We suggest that the integrin alpha v beta 6 is a key component of oral SCC invasion and metastasis through modulation of MMP-3 activity.
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PMID:Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma. 1200 35

Melanomas containing more elastin are associated with higher stages of the disease. The interaction between elastin-derived peptides and melanoma cells appears to play an important role in the progression of melanomas. The effects of the elastin-derived peptides VGVAPG and VAPG have been investigated on the migration, invasion, adhesion and angiogenesis of human melanoma cells of different invasive potential. Elastin, tropoelastin and VGVAPG peptide were demonstrated at the invasion site of melanoma using histochemistry and immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG bind directly to 3 cell surface receptors: galectin-3, integrin alpha v beta 3 and elastin-binding protein. Our results suggest that the increased levels of elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they can increase the migration of melanoma cells and the expression of CXCR-4 and CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the expression of different adhesion molecules; (v) they increase the expression of the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these effects. Clinical and therapeutic aspects are also discussed.
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PMID:Locally generated VGVAPG and VAPG elastin-derived peptides amplify melanoma invasion via the galectin-3 receptor. 1807 73