Expression order of alpha-v and beta-3 integrin subunits in the N-methyl-N-nitrosourea-induced rat mammary tumor model.

We investigated the developmental time course of molecular expression of alpha(v)beta(3) subunits in a carcinogen-induced rat mammary tumor model for human ductal carcinoma in situ (DCIS). Tumors during various stages of growth (from <0.1 to >2.0 cm) were analyzed immunohistochemically for the expression of the alpha(v)beta(3) integrin and its subunits. In general, the expression profiles of these integrin subunits were directly proportional to the size of the tumor. The pattern of immunostaining revealed that anti-alpha(v)beta(3) monoclonal antibody binds to specific sites of tumor sections, forming isolated stained patches. This isolated patch pattern was found in more developed larger tumors. This could be due to the fact that the integrin molecule might be involved in migration and nesting of tumor cells into specific regions to form DCIS or intraductal carcinoma. Results also showed that the alpha(v) subunit expresses earlier than the beta(3) subunit. These data provide insight into tumor cell biology and developmental characteristics that will guide the future construction and use of targeted contrast and therapeutic agents capable of tracking, imaging, or treating a tumor at the earliest stage of formation.