SPP 1190: The Tumour-Vessel Interface
Final Report Abstract
A multitude of cells, molecules and mechanisms controls the complex interactions between the tumor and the vascular compartments to regulate tumor progression and metastasis. While the molecular mechanisms of tumor angiogenesis have been elucidated in substantial detail, much remains to be discovered in the analysis of the intricate bi-directional crosstalk of tumor cells and vessel wall cells during tumor progression and metastasis. Advanced in vitro and in vivo experimental strategies need to concentrate on tumor cells, blood and lymphatic vessel wall cells, and other recruited and resident stromal cells as a dynamic multicompartment cell-cell and cell-matrix interaction and communication system. The intricate interplay between different molecular systems including angiogenic and anti-angiogenic cytokines and their receptors, regulators of the proteolytic balance, adhesion and associated molecules, chemokines and their receptors as well as signaling molecules acting in these cellular compartments awaits detailed molecular and mechanistic analysis. Tumor microenvironmental conditioning by hypoxia and the thrombogenic milieu needs to be studied and its effect on the different cell populations within the tumor must be explored. Interactions between the tumor and the vessel compartment relating to vessel intravasation, systemic dissemination, distant lodging and secondary site growth of metastasizing tumor cells are poorly understood and await molecular characterization. In order to address these key unanswered questions, the Deutsche Forschungsgemeinschaft (DFG) launched the nationwide priority research program SPP 1190 “The tumor-vessel interface”. The SPP has made important and substantial contributions towards the better understanding of tumor progression and metastasis, most notably as it relates to the role of (i) the early dissemination of metastatic cells, (ii) collective cell migration during metastasis, (iii) hypoxia, (iv) redox signaling, (v) chemokines, (vi) ephrin ligands and Eph receptors and other receptor tyrosine kinases, (vii) tumor angiogenesis and lymphangiogenesis as well as (viii) the development of improved imaging modalities and proof-of-principle therapy exoeriments. Beyond promoting tumor progression and metastasis research, the consortium has served important infrastructural and community building purposes by (i) hosting consortium plenary and subgroup meetings, (ii) inaugurating an international tumor progression and metastasis meeting series, (iii) promoting training of the next generation of tumor progression researchers, and (iv) pursuing public outreach activities.
