Tumour Angiogenesis and the VEGF Axis
A tumour cannot grow past about a millimetre without recruiting blood vessels, and it does not build them properly. Hypoxia stabilises HIF-1α, HIF drives VEGF-A, VEGF-A drives VEGFR2, and the vessel that results is leaky, tortuous, poorly perfused and — the part that gets overlooked — actively immunosuppressive. That last property is why anti-angiogenic therapy behaves less like starvation and more like normalisation, and why it combines with checkpoint blockade. Everything on this map follows from one asymmetry: the same signal that makes the vessel also stops immune cells getting through it. Click any protein for the matching Assay Genie ELISA kit, In Vivo antibody or biosimilar.
Oxygen is the switch, and VHL is the reason it works. In normal oxygen, prolyl hydroxylases mark HIF-1α and HIF-2α for destruction and VHL executes it, so HIF protein is almost absent despite being constantly transcribed. Remove the oxygen — or, in clear-cell renal carcinoma, remove VHL by mutation — and HIF accumulates within minutes. That is why kidney cancer is the most VEGF-driven tumour type there is and why it was the first to respond to anti-angiogenic drugs: the switch is stuck on at the top. CA9 and GLUT1 are on this map as the practical readout that the switch is on, because they are HIF targets you can stain for when you cannot measure HIF itself.
The ligand family is not redundant, it is divided by receptor. VEGF-A and PlGF signal through VEGFR1 and VEGFR2; VEGF-B is essentially VEGFR1-only; VEGF-C reaches VEGFR3 and drives lymphangiogenesis rather than blood vessels. The critical distinction is that VEGFR2 carries almost all the pro-angiogenic signalling while VEGFR1 acts largely as a decoy that sequesters ligand. So an anti-VEGF-A antibody and an anti-VEGFR2 antibody are not interchangeable: the first removes one ligand from a family, the second closes the channel every one of them uses. Neuropilin-1 is the co-receptor that raises VEGFR2's affinity without signalling itself, which is why NRP1 loss blunts responses without abolishing them.
Resistance is built into the network, not acquired by mutation. Anti-VEGF therapy rarely fails because VEGFR2 changes; it fails because the tumour switches ligand. FGF2 through FGFR1, PDGF-BB through PDGFR-β, and angiopoietin-2 displacing angiopoietin-1 at TIE2 all reconstitute a sprouting signal that no anti-VEGF agent touches. This is why the field moved to multi-target kinase inhibitors and to ANG2/VEGF bispecifics, and why measuring only VEGF-A in a progressing patient tells you very little. DLL4 and NOTCH1 sit on the map because they do the opposite job: Notch signalling suppresses VEGFR2 in neighbouring cells so that only one endothelial cell per sprout becomes the tip. Block DLL4 and you get more vessels, all of them non-functional.
The vessel is an immune barrier, and that is the part worth measuring. VEGFR2 signalling loosens VE-cadherin junctions (hence oedema and poor drug delivery), induces PD-L1, and downregulates ICAM-1 so that leukocytes cannot arrest and extravasate — endothelial anergy. Add TGF-β acting through endoglin, and CXCL12 holding suppressive myeloid cells in place through CXCR4, and the tumour vasculature becomes an active exclusion zone. Thrombospondin-1 is the endogenous counterweight the tumour has usually silenced. The In Vivo tie-in: nine of 38 nodes carry a functional-grade antibody — the VEGFR2 arm as ramucirumab and as a mouse CD309 antibody, PDGFR-α as olaratumab, plus endoglin, ALCAM, CXCR4, ICAM-1, PD-L1 and pan-TGF-β. This is a more ELISA-led map than most in this library, and deliberately so: the ligands and soluble mediators here are quantitative analytes, not blocking targets. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — ELISA kit, In Vivo antibody or research antibody.