Tumor angiogenesis and tumor growth are accompanied by only a transient increase in platelet rolling in angiogenic microvessels in close vicinity to tumor cells. This might be due to endothelial stimulation by growth factors and cytokines released partly from tumor cells. Within tumor microcirculation, adhesion molecules mediating platelet-endothelial interactions appeared to be downregulated or even absent. Platelet-endothelial interaction in response to endothelial stimulation was significantly reduced in tumor microcirculation.

Future studies are needed to identify mechanisms regulating adhesion molecule expression in tumor microcirculation. Further attempts should focus on induction of platelet aggregation by selective transport of prothrombotic agents into the tumor microcirculation. The results might provide further therapeutic aspects in targeting tumor angiogenesis.


Möhle, R., Green, D., Moore, M. A., Nachman, R. L., and Rafii, S.

(1997). Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc. Natl. Acad. Sei. USA 94, 663-668.

Pinedo, H. M., Verheul, H. M., D'Amato, R. J., and Folkman, J.

(1998). Involvement of platelets in tumour angiogenesis? Lancet 352, 1775-1777. This article proposes a possible role for platelets in tumor

angiogenesis based on a review of the literature, which was the starting point of our experimental work.

3. Carmeliet, P. and Jain, R. K. (2000). Angiogenesis in cancer and other diseases. Nature 407, 249-257.

4. Hammersen, F., Osterkamp-Baust, U., and Endrich, B. (1983). Ein Beitrag zum Feinbau terminaler Strombahnen und ihrer Entstehung in bösartigen Tumoren. In Mikrozirkulation in malignen Tumoren, P. Vaupel and F. Hammersen, eds., pp. 15-51. Basel, CH: Karger. An early publication that already described the absence of platelets in tumor microvasculature.

5. Asaishi, K., Endrich, B., Goetz, A., and Messmer, K. (1981). Quantitative analysis of microvascular structure and function in the amelan-otic melanoma A-Mel-3. Cancer Res. 41, 1898-1904. A detailed, quantitative analysis of tumor microcirculation based on intravital microscopy of a newly developed transparent chamber preparation.

6. Frenette, P. S., Johnson, R. C., Hynes, R. O., and Wagner, D. D. (1995). Platelets roll on stimulated endothelium in vivo: An interaction mediated by endothelial P-selectin. Proc. Natl. Acad. Sci. USA 92, 7450-7454.

7. Konstantopoulos, K., Kukreti, S., and McIntire, L. V. (1998). Biomechanics of cell interactions in shear fields. Adv. Drug. Deliv. Rev. 33, 141-164.

8. Warren, B. A., Shubik, P., and Feldman, R. (1978). Metastasis via the blood stream: The method of intravasation of tumor cells in a trans-plantable melanoma of the hamster. Cancer Lett. 4, 245-251.

9. Salgado, R., Benoy, I., Bogers, J., Weytjens, R., Vermeulen, P., Dirix, L., and van Marck, E. (2001). Platelets and vascular endothelial growth factor (VEGF): A morphological and functional study. Angiogenesis 4, 37-43.

10. Manegold, P. C., Hutter, J., Pahernik, S. A., Messmer, K., and Dellian, M. (2003). Platelet-endothelial interaction in tumor angiogenesis and microcirculation. Blood 101, 1970-1976.

11. Schlingemann, R. O., Rietveld, F. J., Kwaspen, F., van de Kerkhof, P. C., De Waal, R. M., and Ruiter, D. J. (1991). Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. Am. J. Pathol. 138, 1335-1347.

Capsule Biography

Dr. Dellian has been leading a research laboratory on tumor microcirculation and angiogenesis at the Institute for Surgical Research, University of Munich, since 1995. He was introduced to his research by the pioneers in tumor microcirculation, Prof. Konrad Messmer, Prof. Alwin Goetz, and Prof. Rakesh Jain.

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