Osteoblastic bone metastasis is a major complication of prostate cancer. There is currently little insight into the because of bone metastasis, and therapeutic interventions are only temporarily palliative. To investigate this problem, we have developed a series of human prostate cancer xenografts (LAPC) which model the late stages of prostate cancer progression, including bone metastasis and androgen-independent growth. We have used these xenografts to identify molecular pathways which are deregulated in prostate cancer and have begun to create prostate-specific transgenic models based on these findings. Here we will use microPET imaging technologies developed at UCLA to examine the process of prostate cancer metastasis in our animal models.
In Aim 1, we will optimize the visualization of prostate cancer by microPET, using a well characterized models.
In Aim 1, we will optimize the visualization of prostate cancer by microPET, using a well characterized model of osteoblastic metastasis where tumor cells are injected directly into the mouse tibia.
In Aims 2 and 3, we will visualize the process of metastasis prostate gland using the LAPC xenograft model and transgenic mouse models of prostate cancer. We will examine the role of angiogenesis in each step, using VEGF/PET reporter mice from Project 3 (Gambhir). Our ability to serially monitor metastatic tumor growth at different sites will allow us to determine if tissue-specific metastasis is a consequence of selective homing of tumor cells to a particular tissue or selective response of the tumor to growth factors at that site. We will also determine the osteoblastic response is primarily a reaction to the presence of tumor cells or plays a stimulatory role in cancer progression. In addition to providing new mechanistic insights toward the metastatic process, these experiments will establish excellent models to test therapeutic interventions in prostate cancer.
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