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Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement.

Proceedings of the National Academy of Sciences of the United States of America (2009-01-08)
Claudia Fischbach, Hyun Joon Kong, Susan X Hsiong, Marta B Evangelista, Will Yuen, David J Mooney
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Calcium sulfate, ≥99.99% trace metals basis
Sigma-Aldrich
Calcium sulfate, −325 mesh, 99%