Our results suggest that a hypoxic environment may further contribute to successful cancer cell propagation in perivascular pre-metastatic niches by increasing Ang-2 expression in brain microvessels and VEGF expression in brain-invading tumor cells.14–17,44 It is of note that hypoxic conditions may be well tolerated by brain-invading cancer cells, particularly as we detected an increased expression of lactate dehydrogenase A (LDHA) also in early metastatic cancer cells. Here, ANGPT2 is linked to neoplasm.