Transformation of the microvascular system during multistage tumorigenesis.

作者: Eduard Ryschich , Jan Schmidt , Günter J. Hämmerling , Ernst Klar , Ruth Ganss

DOI: 10.1002/IJC.10074

关键词:

摘要: Simian virus SV40 large T Antigen expression in the islets of Langerhans transgenic mice results β-cell hyperproliferation, onset new blood vessel formation and development highly vascularized solid tumors. Angiogenesis RIPTag mouse model, as well human cancer, is a hallmark multistage tumorigenesis precedes In our study, intravital microscopy was used to monitor changes phenotype, microcirculation leukocyte adhesion during progression from normal angiogenic RIP1-Tag5 mice, an aberrant microangioarchitecture becomes apparent early stages spontaneous tumor development. Notably, transition characterized by increase diameter rather than numbers. Thus, dilatation existing vessels sprouting. Once initiated, neovascularization loss hierarchy differentiation. Solid insulinomas display higher density even more dramatic heterogeneity revealed local “hot spots” irregular diameters. Strikingly, profound are already observed suggesting that key features vasculature established prior expansion mass. Moreover, leukocytes found be dramatically decreased both tumors correlates with morphological alterations vasculature. transformation reduced leukocyte-endothelium interactions not exclusively but represent events tumorigenesis. © 2002 Wiley-Liss, Inc.

参考文章(39)
Robert J. Melder, Gerald C. Koenig, Brian P. Witwer, Nina Safabakhsh, Lance L. Munn, Rakesh K. Jain, During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Nature Medicine. ,vol. 2, pp. 992- 997 ,(1996) , 10.1038/NM0996-992
Stefano Martinotti, Cora A. Damen, Gerard Groenewegen, Arjan W. Griffioen, Geert H. Blijham, Endothelial Intercellular Adhesion Molecule-1 Expression Is Suppressed in Human Malignancies: The Role of Angiogenic Factors Cancer Research. ,vol. 56, pp. 1111- 1117 ,(1996)
Gabriele Bergers, Rolf Brekken, Gerald McMahon, Thiennu H. Vu, Takeshi Itoh, Kazuhiko Tamaki, Kazuhiko Tanzawa, Philip Thorpe, Shigeyoshi Itohara, Zena Werb, Douglas Hanahan, Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis Nature Cell Biology. ,vol. 2, pp. 737- 744 ,(2000) , 10.1038/35036374
Thomas Boehm, Judah Folkman, Timothy Browder, Michael S. O'Reilly, Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance Nature. ,vol. 390, pp. 404- 407 ,(1997) , 10.1038/37126
Noël Bouck, Veronica Stellmach, Stephanie C. Hsu, How Tumors Become Angiogenic Advances in Cancer Research. ,vol. 69, pp. 135- 174 ,(1996) , 10.1016/S0065-230X(08)60862-3
Sareh Parangi, Gerhard Christofori, William Dietrich, Eric S. Lander, Douglas Hanahan, Tumor suppressor loci on mouse chromosomes 9 and 16 are lost at distinct stages of tumorigenesis in a transgenic model of islet cell carcinoma. Cancer Research. ,vol. 55, pp. 6071- 6076 ,(1995)
Rakesh K. Jain, Determinants of Tumor Blood Flow: A Review Cancer Research. ,vol. 48, pp. 2641- 2658 ,(1988)
Ruth Ganss, Douglas Hanahan, Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes Cancer Research. ,vol. 58, pp. 4673- 4681 ,(1998)
S. Bonner-Weir, L. Orci, New Perspectives on the Microvasculature of the Islets of Langerhans in the Rat Diabetes. ,vol. 31, pp. 883- 889 ,(1982) , 10.2337/DIAB.31.10.883