Assessment and Prognosis of Prostate Cancer Metastasis
Prostate cancer is the second leading cause of malignancy-related mortality in males. Prostate cancer cells spread to liver, lungs, and especially bone via the blood stream and form secondary tumors in these organs. Bone metastases are incurable and a major complication of prostate cancer patients. Cancer cell motility towards increasing concentrations of certain chemicals plays an important role in metastases. Several chemicals such as chemokines and growth factors are believed to influence the migration of prostate cancer cells. Despite improvement in clinical response rates with newly developed targeted multi-kinase inhibitors, death due to metastases remain major impediments to its cure. With a focus on the development of new inhibitors, particularly, RLIP76 blockade has been shown highly effective. The findings are potentially of major clinical significance because they promise a unique, highly effective and functionally cancer-specific targeted therapy.  However, limitation of available tools has resulted in inadequate knowledge about the dynamic effects of the chemical gradients on prostate cancer migration and related proteomic mechanisms at the cellular level responsible for metastasis. In this collaborated project, we have developed a novel assay that integrates the microfluidic cell migration platform and ultra sensitive silicon nanowires field-effect transistor biomarker sensors to study cancer cell migration associated with prostate cancer metastasis. The high-throughput arrayed microfluidic assays have been demonstrated for feasibility, and utilized for studying prostate cancer cell migration dynamics in our experiments. The devices have a capacity of assaying individual chemokines and their combinations, with and without the knockdown of RLIP76, in a parallel and time-lapsed fashion. Both mesangial and cancer cells were tested. Four markers were tested in multiple experiments and the effects were found as: HNE (mesangial: attract, cancer: inhibit), GSHNE (mesangial: attract, cancer: attract), IL-7 (mesangial: inhibit, cancer: inhibit), anti-RLIP76 (mesangial: inhibit, cancer: inhibit). The data gathered can provide important information in designing anti-metastasis drugs. More importantly, our devices are proven to have ability to assay the metastatic markers and provide time-lapsed information of prostate cancer cell migration.  The devices can be used in many applications to assay the cellular and molecular responses in cell migration.  

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