Tumour reactions to hypoxia

Fast growing solid tumors generally lack an inner organisation, which causes the problem of a sufficient nutrient of each part of the tumor that then happens only by diffusion. The low oxygen supply leads to the activation of hypoxia-inducible factors, which regulate a plethora of genes. The reaction of tumor cells to hypoxia can be divided into two parts: On the one hand, there are signal substances, predominantly growth factors and cytokines, which provoke the vascularisation (angiogenesis), lymph vessel development (lymphangiogenesis), and the innervation (neoneurogenesis) of tumors and thus connect the tumor to structures of the environment. On the other hand, genes for intracellular proteins and receptors are regulated, which lead to changes of the tumor cell functions. Best characterized is the metabolic shift, a high anaerobic glycolytic activity and simultaneously a reduction of respiration. Furthermore, proliferation, dedifferentiation, resistance to apoptosis, and the metastatic potential are affected. With regard to the latter, we herein show that the migratory activity and velocity of PC-3 human prostate carcinoma cells significantly increases under oxygen-deprivation, which might be an explanation for the increasing number of experimental and clinical hints, that an anti-angiogenic therapy can promote the metastasis formation.