Contribution of bone marrow-derived cells to tumor progression and metastasis. Cells recruited to the tumor microenvironment, in particular BMDC and inflammatory cells, contribute to tumor progression, by establishing paracrine relationships with the tumor cells. In particular monocytes/macrophages, are important sensors of tissue hypoxia and necrosis. We are characterizing the mechanisms of mobilization of these cells, their contribution to local tumor growth and their role in generating premetastatic niches.
Inflammatory mechanisms of tumor promotion. Inflammation promotes tumor progression through various mechanisms including expression of COX-2 and prostaglandin production. COX-2 acts as tumor promoter by inducing angiogenesis and stimulating tumor cell survival and motility. We are interested in identifying downstream target genes of COX-2 and molecular mediators of its effects on endothelial cells and tumor cells.
Radiation-induced stroma remodeling in invasion and metastasis. Radiotherapy is successfully used to treat a variety of cancers, but recurrence after radiotherapy are associated with increased local invasion, metastatic spreading and poor prognosis. While it is generally assumed that the increased aggressiveness of relapsing tumors is due to the selection of tumor cells resistant to radiation-induced apoptosis, recent results indicate that irradiated stroma promotes tumor progression and metastasis. We are interested in understanding the mechanisms responsible for this effect. Recent work has identified the matricellular protein CYR61 and its receptor integrin alphaVbeta5 as critical mediators of metastasis of tumors growing in irradiated fields.