The growth of a tumor goes along with various changes in the tumor blood supply. On the one hand, tumor progression leads to the formation of new vessels in the tumor stroma (angiogenesis). On the other hand, an enhanced tumor perfusion can only be realized by an adaptive growth (arteriogenesis) of arteries that supply the tumor - an often largely ignored circumstance.

In order to investigate the interdependence of tumor perfusion and tumor growth in vivo, we established a novel orthotopic tumor mouse model. Therefore, a single tumor spheroid consisting of a defined number of B16 melanoma cells was subcutaneously inoculated in the mouse auricle; after about two weeks, a locally defined melanoma developed. From then on, we were able to progressively follow the complete tumor and vascular development including the tumor-induced adaptive growth of peripheral blood vessel within about four weeks. Additionally, this tumor model enabled us to topically administer drugs - for example decoy oligodesoxynucleotides (dODN) - to manipulate the tumor progression.

Notably, the transdermal application of a dODN that neutralizes the function of the activator protein-1 (AP-1) - a transcription factor that is key critical for the adaptive growth of arteries and veins - delayed the tumor manifestation and inhibited the tumor progression. Further in vitro experiments showed, that the AP-1 dODN neither directly affected the proliferation and the cytokine release of the melanoma cells, nor influenced the tumor angiogenesis. We therefore assume that the tumor progression correlates with an AP-1-dependend growth of tumor-supplying arteries and arterioles.