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Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma.
- Source :
-
Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2002 Apr; Vol. 21 (3), pp. 297-307. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- 3T3 Cells
Animals
Basement Membrane
Carcinoma, Squamous Cell metabolism
Cell Adhesion
Cell Division
Cell Line
Cell Movement
Dipeptides pharmacology
Extracellular Matrix metabolism
Fibronectins metabolism
Humans
Matrix Metalloproteinase 3 metabolism
Metalloendopeptidases antagonists & inhibitors
Mice
Mice, Nude
Mouth Neoplasms metabolism
Neoplasm Invasiveness
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Antigens, Neoplasm genetics
Carcinoma, Squamous Cell pathology
Gene Expression
Integrins genetics
Mouth Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0945-053X
- Volume :
- 21
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Matrix biology : journal of the International Society for Matrix Biology
- Publication Type :
- Academic Journal
- Accession number :
- 12009335
- Full Text :
- https://doi.org/10.1016/s0945-053x(02)00002-1