Cancer Microenvironment and Therapeutic Implications---A Systematic Approach to Investigate the Interplays between Cancer Cell and Haemostatic System

Despite improvements in diagnosis, surgical techniques, and local and systemic adjuvant therapies, most of the cancer deaths result from the progressive growth and metastasis with cancer cell colonized at multiple organs. Understanding the process of how cancer cells outgrow and escape from the primary site is important for development of novel therapeutic approach. Abnormal coagulation profiles have been found in cancer patients. Haemostatic activation may promote cancer metastasis and induce thromboembolism complication. Many studies point out that cancer cells could produce procoagulant proteins, activate platelets and thrombus formation. Local or systemic hypercoagulability facilitates the aggressive biology of cancer and confer a growth advantage to tumor cells. Accordingly, cancer cell-platelet interactions as well as cancer cells and host cell-derived microparticles have been shown to play a critical role for metastatic cells to survive in bloodstream and colonize distant target organs, although the detailed molecular mechanisms still need to be explored. Hence, the pathophysiological effects and the therapeutic implications of blood coagulation activation on cancer metastasis will be investigated in this three-year program project. In addition to the Core project, each of the 4 subprojects will be led by an experienced principle investigator to explore the interplays between cancer cells and haemostatic system. Dr. Ching-Ping Tseng, a molecular and cellular biologist focusing on cancer and platelet biology, will lead the program project and will explore the molecular and functional insight for the novel regulators that are implicated in cancer cell-platelet interactions and cancer progression. Dr. Jau-Song Yu, a biochemist interested in signal transduction biology and cancer biomarker discovery using proteomic technology, will discover novel regulators and biomarkers in cancer progression based on comprehensive profiling of cancer cell-derived secretomes and microparticles. Dr. Chin-Ming Tan, a molecular biologist interested in chromatin biology and epigenetic gene regulation, will characterize the gene expression network that underlies cancer cell-platelet interactions and cancer progression. Dr. Kowit-Yu Chong, a stem cell biologist interested in applying genetic modification approaches for disease therapy, and Dr. Chang-Hui Liao, a pharmacologist interested in platelet physiology and the therapeutic effect of natural products/compounds in thromboembolic complications, will develop innovative cancer therapeutic regimens by blockage of cancer cell-mediated activation of platelet and coagulation cascade. Briefly, each subproject has their own role in discovery phase (subproject 1), molecular and cellular study (subprojects 2 and 3) and translational phase (subproject 4), whereas these subprojects together will fulfill the program project goals and provide us a comprehensive and contemporary overview regarding the functional role of haemostatic system in cancer progression. The accomplishment of this program project may also lead to discovery of novel gene products that are useful for diagnosing and monitoring cancers and development of effective targeting gene therapy.

Project ID:PC10101-1279
External Project ID:NSC99-2632-B182-001-MY3