A4: Interaction of inflammatory stroma and tumor cells in pancreatic cancer
Pancreatic cancer is characterized by the presence of a profound desmoplastic reaction and inflammatory infiltrates. Among other, tumor-associated macrophages (TAMs) are known to influence tumor progression via a cytokine-mediated interaction with tumor cells. Previously, we identified the transcription factor Cut-like-1 (CUTL1, also known as CUX1) as crucial modulator of tumor cell motility and invasion. Interestingly, CUTL1 is highly expressed in both tumor cells and adjacent tumor-associated macrophages. Initial co-culture experiments suggest that CUTL1 expressed in TAMs stimulates proliferation and migration of neighbouring pancreatic cancer cells. Based on these observations, the aim of the project is to elucidate the effect of TAMs and signalling pathways including CUTL1 on the proliferation and invasion of pancreatic cancer cells in vitro and in vivo. This includes:

I) characterization of the upstream regulation of CUTL1 by cytokines and growth factors involved in the differentiation of TAMs,

II) identification of the CUTL1-induced cytokine-profile mediating its effects on tumor cells,

III) the in vivo evaluation of CUTL1 effects in TAMs in a xenograft mouse model,

IV) evaluation of the effects of TAM´s and their therapeutic modulation in genetic mouse models of pancreatic cancer.

 

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Last Updated on Friday, 17 July 2009 09:07