Integrin receptors play an important role in cell adhesion, migration, invasion, metastasis, homing and signalling. These cell surface receptors are composed of a single alpha and a single beta subunit and bind to extracellular matrix components such as fibronectin, vitronectin, laminin and collagen. Integrins containing the alpha-v subunit when expressed in malignancies such as melanoma play a role in invasion and metastasis. I have described the expression of a recently identified alpha-v containing integrin receptor, alpha-v-beta8, in melanoma cell lines and have characterized it as a vitronectin receptor. How does alpha-v-beta8 contribute to the ability of the melanoma cell to adhere to, migrate on and proliferate in response to vitronectin? Does alpha-v-beta8 bind to ligands other than vitronectin? How does the unique structure of beta8 relate to its function? Why does the melanoma cell express multiple vitronectin receptors and how does their expression correlate to the invasive phenotype? To answer these questions I will evaluate the function of beta8 normally expressed in melanoma cell lines and overexpressed in transfected melanoma cell lines which normally do not express the beta8 subunit. I will evaluate the ability of the beta8 transfected cells to adhere to and to migrate on vitronectin in adhesion and migration assays. Evidence has shown that integrins may stimulate cell proliferation. I will use beta8, transfected melanoma and 293 cells to evaluate cell proliferation in 3 dimensional gel systems. I will test the ability of beta8 transfected melanoma and 293 cells to invade through membranes using a variety of invasion as says. Finally, I will perform immunohistochemical analysis on melanoma specimens and will assess a-v integrin expression. These studies will provide valuable information into the function and biologic importance of a newly described integrin adhesion receptor and will provide the excellent training necessary for making the transition to scientific independence.
| 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 |
| Nishimura, S L; Broaddus, V C (1998) Asbestos-induced pleural disease. Clin Chest Med 19:311-29 |
