Elucidating the role of L1CAM during the development of ovarian carcinoma

• Applicant: Dr. Kai Doberstein
• Subject Area: Gynaecology and Obstetrics
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264428931

Ovarian cancer is one of the leading causes of cancer mortality among women and it remains often undetected until late-stage metastatic disease. Especially the most abundant subtype of high-grade serous ovarian carcinoma (HGSOC) was shown to have the worst prognosis. Most of these tumors recur in a chemoresistant form and diagnostic and therapeutic options are limited . Therefore, new and more effective diagnostic and therapeutic target molecules are urgently needed. Recent findings have shown that HGSOC originate not from the ovarian surface epithelium, but from the fimbria of the fallopian tube. This new model of pathogenesis gives the possibility to discover new biomarkers and therapeutic targets for HGSOC.The cell adhesion molecule L1CAM has been demonstrated to be involved in many aspects of cancer development i.e. chemoresistance, cell migration and invasion, gene regulation, EMT and proliferation. L1CAM is abundantly expressed in HGSOC and is associated with poor overall survival. Recently, our preliminary data have shown that L1CAM is expressed in preneoplastic lesions of the fimbria. Our hypothesis is that the expression of L1CAM in preneoplastic lesions might be an important step for the malignant transformation of fallopian tube cells to HGSOC.Therefore, we propose to study the L1CAM expression at all stages of human HGSOC using clinical samples to find out at which stage of the disease the progression of L1CAM becomes elevated. We also wish to study whether the expression of L1CAM can transform fallopian tubular cells to a malignant and tumorigenic state by using a unique mouse model and human fallopian tubular cells. Elucidating the role of L1CAM during the development of HGSOC could help to develop new treatment strategies and might help to diagnose the disease at an earlier stage.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ronny Drapkin