M.J. Voss, B. Niggemann, K.S. Zanker and F. Entschladen Pages 381 - 386 ( 6 )
Fast growing solid tumours generally lack an inner organisation, which causes the problem of a sufficient nutrient of each part of the tumour 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 tumour 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 tumours and thus connect the tumour to structures of the environment. On the other hand, genes for intracellular proteins and receptors are regulated, which lead to changes of the tumour cell functions. Best characterised 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 increase under oxygendeprivation, which might be an explanation for the increasing number of experimental and clinical hints, that an anti-angiogenic therapy can promote the metastasis formation.
Hypoxia, angiogenesis, lymphangiogenesis, neoneurogenesis, metabolic shift, cell migration, metastasis formation
Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany.