|
| LEC integrins | Matrix ligands | Data implicating integrin in lymphangiogenesis | Current inhibitors FDA approved or in clinical trials |
|
| α1β1, α2β1 | Collagens | Overexpressed in LEC treated with VEGF-A [13]; blocking antibodies reduce lymphangiogenesis in wound healing [13]; corneal inflammation models [14] | None |
|
| α5β1 | Fibronectin | Expressed in sprouting LECs [15]; small molecule inhibitors reduce lymphangiogenesis in cornea [15]; lung inflammation models [16] | Volociximab
PF-04605412
JSM6427
[17–19] |
|
| αvβ3, αvβ5 | Fibronectin (RGD),
Osteopontin,
Vitronectin,
Fibrinogen
Fibrillin | Minimal expression in LECs [20];
no role in lymphangiogenesis described to date [20, 21] | Cilengitide,
CNTO95
EMD525797
IMGN388
[17–19] |
|
| α9β1 | Fibronectin (EDA),
Osteopontin,
Tenascin-C,
VEGF-A/C/D | Knockout mice die postnatally due to defective lymphatic valve development (lung chylothorax) [22–24];
binds directly to VEGF-A/C/D and blocking antibodies inhibit LEC migration [25, 26];
endostatin (α5β1 and α9β1 inhibitor) blocks lymphangiogenesis in cancer models [27, 28] | None |
|
| α4β1 | Fibronectin (CS1),
Osteopontin,
Emillin-1 | Not required for developmental lymphangiogenesis [29];
expressed in tumor-associated lymphangiogenic vessels and in proliferating LECs [20, 29];
blocking antibodies prevent VEGF-C-induced LEC migration [20, 29]; knockout and dominant negatives block tumor lymphangiogenesis [29] | Natalizumab
Vedolizumab
ELND002
[17–19] |
|
| α6β1 | Laminin,
Netrin-4 | Mediates LEC adhesion and migration to prolymphangiogenic factor Netrin-4 [30, 31]; colocalizes with netrin-4 in lymphangiogenic vessels associated with breast tumor xenografts [30] | None |
|
