Research Axis
Fetomaternal and Neonatal Pathologies Axis
Research Theme
Fetal development and prematurity
Address
CHUSJ - Centre de Recherche
Phone
514 345-4931 #3656
Fax
514 345-4801
Emerging role for cell-derived microparticles in cancer therapy
One of the major distinguishing features of today’s pharmacology is the drive to produce multiple therapeutic approaches against an illness. For example, against cancer, some will call on inhibitors at different stages of cellular production, while others will try to asphyxiate tumors by impeding blood vessel proliferation. The lymphocyte-derived microparticles (LMP) present themselves to some extent as cellular residues from lymphocytes. LMP present a new line of attack on two fronts against breast cancer. First LMP can fight cellular proliferation and second LMP promise to exert an anti-angiogenic action. One of the problems of chemotherapy is the enormous secondary effects it causes in patients because it also attacks non-cancerous cells. This is where LMPs could make a big contribution. They don’t kill cancerous cells, but they could halt their proliferation. That means that chemotherapy, from one treatment to another, could be shortened and prove much less taxing for patients because LMPs could have blocked the increase of cancerous cells between treatments. The industrial production of LMPs is relatively easy and their manufacturing cost low. A different route to mass production is also possible through personalized therapies, one of the more exciting potentials of these particles. They open the door to treatments tailor-made for each patient. We could take blood from the patient, extract the lymphocytes and, after having cultivated and treated them to obtain microparticles, reinject them into the patient. The risk of rejection and of many secondary effects would thus be reduced.
Effects of lymphocyte-derived microparticles in angiogenesis
Our current findings provide evidence for the first time, that lymphocyte-derived microparticles (LMPs) inhibit vascular angiogenesis by affecting both proliferation and migration of endothelial cells, without increasing apoptosis and necrosis. Our results also suggest that LMPs may act through oxidative stress and VEGF signaling pathways to modulate angiogenesis. The central role of VEGF in angiogenesis makes it attractive as a therapeutic target for anti-angiogenic drugs. Understanding how LMPs interrupt VEGF signaling will provide therapeutic strategies aimed at reducing the abnormalities of neovascularization in different pathological processes.
Role of CD36 (scavenger receptor) in corneal neovascularization
Our work provide the first demonstration of the protective involvement of CD36 in limiting inflammatory CNV. Other anti-angiogenic factors such as endostatin, thrombospondin, PEDF, and maspin have also been found in the uninjured cornea, reaffirming the importance of these types of factors in maintaining transparency of the healthy cornea. Our observations have significant implications for the treatment of ocular neovascularization in that CD36 stimulants would be effective not only in patients with ongoing CNV, but also in those presenting established CNV. Findings may not only apply to corneal inflammation following injury or infection, but may also be relevant in corneal graft failure which involves an inflammatory immune rejection.