Non-NE cells up-regulated the hypoxia-responsive TF FOXC2 (Fig. 4H), a key driver of VM and resistance to anti-angiogenic therapy in aggressive tumor subtypes.46 Hypoxia promotes VM in melanoma, colorectal cancer, and Ewing sarcoma,20,50,51 and although SCLC is fast-growing and typically hypoxic,64 network formation by non-NE cells occurred in oxygenated Matrigel. This evidence concerns the gene FOXC2 and melanoma.