We developed a screening in which peptides that home in vivo to specific tissues are selected that administration of a peptide library. We also developed methods for determining the distribution in vivo of such targeted probes and cellular receptors. Moreover, we have defined specific differences in the normal microvasculature and elucidate multiple abnormalities in tumor blood vessels. Taken together, this work revealed the molecular diversity of blood vessels and uncovered a vascular address system. This system allows organ-specific targeting to normal blood vessels and understanding of zonal differences in the normal prostate microenvironment, changes in the prostate stroma during tumor progression, and the localization of novel vascular markers in prostate cancer. We hypothesize that the vascular endothelium of the prostate is modified in a tissue-specific manner and that the development of prostate cancer is accompanied by abnormalities in the vasculature. Such heterogeneity may affect the responses to therapies; our goal is the prostate with a focus on the angiogenic vasculature of prostate cancer. These data will identify diagnostic and prognostic factors, and to design novel targeted strategies against prostate cancer. These data will identify diagnostic and prognostic factors, and to design novel targeted strategies against prostate cancer.
Our Specific Aims are (i) to image the vascular morphology of normal prostate and during the progression of prostate cancer, (ii) to identify homing-peptides to blood vessels in the normal prostate and in prostate cancer, (iii) to define molecular changes in the vasculature during the progression of prostate cancer by using tissue- specific and angiogenesis-related markers of blood vessels, and (iv) to use targeting peptides for delivery of therapeutic agents to the vasculature in prostate cancer. In addition to providing cancer microenvironments. Novel prostate vascular receptors may shed light in the complex cellular diversity of prostate cancer. Unique and highly attractive feature of these functional assays is that they detect the availability of targets based not only on tissue expression level, but also on accessibility to a circulating probe. We will seek to validate these probes as delivery vehicles in targeting approaches of prostate cancer.
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