Angiogenesis/Vasculogenesis in solid tumors
The neo-angiogenesis process is crucial for solid tumor growth and invasion, as the vasculature provides metabolic support and access to the circulation. Endothelial cells present in tumors possess a distinct and unique phenotype differing from normal endothelial cells at the molecular and functional levels, they are genetically unstable and may acquire resistance to drugs. Recent data of the literature suggest alternative strategies of tumor vascularization in respect to normal angiogenesis. Normal endothelial cells might be reprogrammed to a more angiogenic or de-differentiated phenotype by genetic information transmitted from the tumor. Reported mechanisms are the phagocytosis of tumor apoptotic bodies or mRNA/microRNA transfer by exosomes/microvesicles released by tumor cells. In addition, it has been shown that at least part of the tumor vessels may derive from an intra tumor ongoing embryonic-like vasculogenesis. This might be due to the differentiation of normal resident or circulating stem cells or of tumor-initiating stem cells. Recent data of the literature and from our group indicate that the mechanism of tumor angiogenesis is not solely dependent on recruitment of normal endothelial cells.
In particular, it can be schematized that vessels in the tumor derive from
i) recruitment of normal endothelial cells,
ii) reprogramming of normal endothelial cells by transfer of genetic material (mRNAs and microRNAs, oncogenes) mediate by exosomes/microvescicles from tumor cells or stem cells,
iii) endothelial differentiation of resident/circulating stem cells,
iv) endothelial differentiation of tumor stem cells,
v) cell fusion.
An increasing amount of data proposes these different strategies as responsible of a distinct and unique phenotype of tumor endothelial cells. Of particular relevance are the novel findings on the endothelial differentiation of tumor stem cells. These mechanisms might explain the notion that tumor endothelial cells are different from normal endothelial cells, the genetic abnormalities observed in these cells as well as the resistance to anti-angiogenic therapy.
- to dissect the different potential mechanisms involved in the formation of vessels within solid tumors, with regard to angiogenesis and vasculogenesis.
- dissect the alternative mechanisms involved in tumor vascularization and the mechanisms that may support and favour the different origin of vessels.