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 αvβ3 subunits in a carcinogen-induced rat mammary tumor model for human ductal carcinoma in situ (DCIS). Tumors during various stages of growth (from 2.0 cm) were analyzed immunohistochemically for the expression of the αvβ3 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-αvβ3 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 αv subunit expresses earlier than the β3 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

Optical micro-scale mapping of dynamic biomechanical tissue properties

Mechanical forces such as adhesion, shear stress and compression play crucial roles in tissue growth, patterning and development. To understand the role of these mechanical stimuli, it is of great importance to measure biomechanical properties of developing, engineered, and natural tissues. To enable these measurements on the micro-scale, a novel, dynamic, non-invasive, high-speed optical coherence elastography (OCE) system has been developed utilizing spectral-domain optical coherence tomography (OCT) and a mechanical wave driver. Experimental results of OCE on silicone phantoms are in good agreement with those obtained from a standardized indentation method. Using phase-resolved imaging, we demonstrate OCE can map dynamic elastic moduli of normal and neoplastic ex vivo human breast tissue with a sensitivity of 0.08%. Spatial micro-scale mapping of elastic moduli of tissue offers the potential for basic science and clinical investigations into the role biomechanics play in health and disease

Fc-directed antibody conjugation of magnetic nanoparticles for enhanced molecular targeting

In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs) functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody to target the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aids their efficient immunospecific targeting through free Fab portions. The directional specificity of conjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophages treated with functionalized MNPs and free anti-HER2 antibody revealed that the antibody molecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe for molecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression