The applicant has identified the beta6 subunit, showed it forms heterodimers with alphav, and functions as a fibronectin receptor. Moreover, its expression is limited to epithelia and increases dramatically during development, wound healing, inflammation, and during malignant transformation. The largest expression of alphavbeta6 is found at invasive edges of carcinomas, and the applicant has found that transfection of beta6 in to colon cancer cells increases their proliferation in a collagen gel. Based on these data, he hypothesizes that alphavbeta6 plays a critical role in the invasive growth of carcinomas cells in vivo. To test this hypothesis, he will examine the migration of carcinoma cells out of freshly explanted tumors into a three dimensional collagen-fibronectin matrix. He will examine the distribution of alphavbeta6 under these conditions, and determine whether antibodies to alphavbeta6 interfere with migration. He will then characterize a series of mouse lines expressing oncogenes such as c-neu, c-src, and polyoma middle T under control of mouse mammary tumor virus promoter. The distribution of alphavbeta6 in tumor tissue of these mice will be analyzed and correlated with tumor progression in oncogene expression. Finally, these mice that develop beta6 positive tumors will be crossed with beta6 null mice, to determine whether some difference in tumor cell behavior is observed.
| Xue, H; Atakilit, A; Zhu, W et al. (2001) Role of the alpha(v)beta6 integrin in human oral squamous cell carcinoma growth in vivo and in vitro. Biochem Biophys Res Commun 288:610-8 |
| Nishimura, S L; Boylen, K P; Einheber, S et al. (1998) Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat brain. Brain Res 791:271-82 |
| Marazzi, S; Blum, S; Hartmann, R et al. (1998) Characterization of human fibroleukin, a fibrinogen-like protein secreted by T lymphocytes. J Immunol 161:138-47 |
| Erle, D J; Pytela, R (1992) How do integrins integrate? The role of cell adhesion receptors in differentiation and development. Am J Respir Cell Mol Biol 6:459-60 |
| Busk, M; Pytela, R; Sheppard, D (1992) Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein. J Biol Chem 267:5790-6 |
