Tumor progression, invasion and ultimately metastasis result from interactions between cancer cells and their supporting stromal microenvironment. The tumor stromal microenvironment share many similarities with fibrotic stroma and comprises extracellular matrix components, as well as cellular components such as stromal cells (fibroblasts and myofibroblasts), blood and lymphatic vessels, and immune cells, which are collectively modulated by the tumor to allow progression and invasion. Our team is interested in the stromal crosstalk with tumor cells and immune cells, and how dysregulation of these interactions contribute to disease pathogenesis.
Our previous investigations highlighted the critical role of ADAM9 (A Disintegrin And Metalloprotease 9) in prostate tumor progression, possibly by altering the tumor-stromal crosstalk through shedding of growth factors essential in tumor proliferation and differentiation (such as EGF and FGFR2iiib). A similar role was found for ADAM12, highly expressed by a subset of carcinoma-associated stromal cells.
Stromal cells developing in tumors can be visualized by staining with antibodies against PDGFRa, aSMA, FAP, gp38, desmin, vimentin, and other stromal markers. A major current focus of our team is to understand the mechanisms by which functionally distinct subsets of stromal cells develop, differentiate and affect tumor progression/immunity. We are investigating different tumor microenvironment, including breast cancer, pancreatic cancer and melanoma, as well as metastasis in the lymph node, lung and liver to assess stromal organ specificities. Using transgenic mice generated in the lab, we are currently identifying mechanisms underlying the contribution of subsets of stromal cells to tumor angiogenesis, immune responses and therapeutic resistance, as increasing evidence indicates that stromal cells may contribute to a lack of response/ resistance to anti-cancer therapies.(A) Stromal cells (red) supportive of leucocytes (green) developing in the periphery of a neuroendocrine pancreatic tumor (blue), (B) stromal cells (red) infiltrating a poorly differentiated prostatic carcinoma (gray) and producing collagen (blue) and proteases (green). (credit: L. Peduto, Institut Pasteur)