| Title | Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement |
| Publication Type | Journal Article |
| 2009 |
| Authors | Fischbach, C, Hyun, JK, Hsiong, SX, Evangelista, MB, Yuen, W, Mooney, DJ |
| Journal | Proceedings of the National Academy of Sciences of the United States of AmericaProc. Natl. Acad. Sci. U. S. A. |
| Volume | 106 |
| Issue | 2 |
| Pagination | 399 - 404 |
| Date Published | 2009/// |
| 00278424 (ISSN) |
| animal experiment, animal model, Animals, arginylglycylaspartic acid, article, bone marrow transplantation, cancer cell, cancer cell culture, Cell Culture Techniques, concentration (parameters), controlled study, cytokine release, Diffusion, Drug delivery, ECM, Humans, hydrogel, Hydrogels, IL-8, implantation, in vivo study, integrin, Integrins, interleukin 8, Interleukin-8, Mice, microenvironment, Models, Biological, mouse, Mus, Neoplasms, Neovascularization, Pathologic, nonhuman, polymer, priority journal, signal transduction, systemic circulation, Tumor vascularization, upregulation, Vascular Endothelial Growth Factor A, vasculotropin |
| Three-dimensional culture alters cancer cell signaling; however, the underlying mechanisms and importance of these changes on tumor vascularization remain unclear. A hydrogel system was used to examine the role of the transition from 2D to 3D culture, with and without integrin engagement, on cancer cell angiogenic capability. Three-dimensional culture recreated tumor microenvironmental cues and led to enhanced interleukin 8 (IL-8) secretion that depended on integrin engagement with adhesion peptides coupled to the polymer. In contrast, vascular endothelial growth factor (VEGF) secretion was unaffected by 3D culture with or without substrate adhesion. IL-8 diffused greater distances and was present in higher concentrations in the systemic circulation, relative to VEGF. Implantation of a polymeric IL-8 delivery system into GFP bone marrow-transplanted mice revealed that localized IL-8 up-regulation was critical to both the local and systemic control of tumor vascularization in vivo. In summary, 3D integrin engagement within tumor microenvironments regulates cancer cell angiogenic signaling, and controlled local and systemic blockade of both IL-8 and VEGF signaling may improve antiangiogenic therapies. © 2009 by The National Academy of Sciences of the USA. |
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