Lymphangiogenesis inhibitors for cancer and for graft survival
Compositions and methods are provided for treating and/or preventing lymphangiogenesis in a subject by using an inhibitor of a galectin-8 protein in an amount effective to inhibit or to modulate an activity of the galectin-8 protein or a portion thereof sufficient to inhibit the lymphangiogenesis associated with cancer, corneal injury, dry eye disease, inflammation, lymphedema, organ rejection or graft rejection.
1. A method for treating or preventing lymphangiogenesis in a subject, the method comprising:
selecting an inhibitor of a galectin-8 protein or a portion thereof, wherein the inhibitor is a dominant negative inhibitor or a saccharide inhibitor selected from Thymine DNA glycosylase (TDG), 3′-sialyl lactose, and Maackia amurensis II (MAA II);
administering a therapeutically effective amount of a pharmaceutical composition to the subject, wherein the composition comprises the inhibitor; and,
measuring a decrease in a lymphangiogenesis marker in the subject.
2. The method according to claim 1 further comprising, analyzing an amount or an activity of at least one of the lymphangiogenesis marker selected from: podoplanin (PDPN),LYVE-1, PROX-1, desmoplakin, VECGF-C, VEGF-D receptor, and VEGFR-3.
3. The method according to claim 2 , wherein analyzing further comprises measuring the treating or the preventing of lymphangiogenesis in the subject.
4. The method according to claim 1 further comprising, measuring interaction between at least two of the following: galectin-8 protein, VEGFR-3, and PDPN.
5. The method according to claim 4 further comprising, measuring binding of the composition to the galectin-8 protein thereby modulating a VEGF-C/VEGF receptor-3 pathway and/or a PDPN pathway in the subject.
6. The method according to claim 1 wherein the lymphangiogenesis is associated with a cancer, a corneal injury, a dry eye disease, an inflammation, a lymphedema, or a graft rejection.
7. The method according to claim 1 , wherein administering further comprises topical delivery or transscleral delivery by a route selected from the group of: passive diffusion, osmotic pump, iontophoresis, ocular implant, or controlled release device.