Role of tumor associated pericytes in pancreatic cancer: a comprehensive evaluation of pericyte function in tumor progression and metastases and the impact of a targeted therapy against pericytes in orthotopically induced and spontaneous pancreatic primary tumor mouse models

• Applicant: Professor Dr. Christoph Kahlert
• Subject Area: General and Visceral Surgery
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 211240916

Active components of the tumor stroma such as fibroblasts, endothelial cells, pericytes or leukocytes have all been implicated to play an important role during tumor progression and metastasis. The tumor microenviroment is importantly involved in (neo-)angiogenesis to provide tumor cells with oxygen and nutriments. In this context, pericytes play a pivotal role since they cover the capillaries of the tumor and support the blood supply of cancer cells. Several publications have suggested that targeting pericytes likely decreases tumor angiogenesis and inhibits tumor growth. However, preliminary data suggests that depletion of pericytes leads to significant elevation in tumor hypoxia, elevated HIF-1a, tortuous and leaky blood vessels, high level of epithelial-to-mesenchymal transition (EMT) and enhanced metastasis. Therefore, it is imparative that before clinical trials are conducted with anti-PDGFRb agents, pre-clinical studies are performed to address the impact of pericyte ablation on myriad of tumor associated events including metastasis.The aim of this study is to investigate the role of pericytes in in orthotopically induced and spontaneous pancreatic primary tumor mouse models and their impact on tumor progression and metastases. A comprehensive analysis of a targeted therapy against pericytes using novel transgenic mice or pharmacological ablation by imatinib mesylate or SU6668 will be conducted. Hence, this research project will unravel mechanism-based, target-validated, combination therapies for metastatic pancreatic cancer and characterise a risk profile of a targeted therapy against pericytes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Raghu Kalluri