(184a) Effects of Hypoxic, Aligned Collagen Gels on Sarcoma Cell Proliferation and Invasion

Orientation of collagen fibers has proven to affect cell proliferation and adhesion to in vitro

scaffold. More understanding of this effect on malignant cancers, like sarcoma, is desirable,

especially under hypoxic conditions that many sarcoma tumor masses possess. Here, we

evaluate the consequences of three-dimensional aligned collagen I fibers in extracellular matrix

(ECM) on sarcoma cell proliferation and invasion in hypoxic regions. Applying a unidirectional

compression on collagen gel has shown to increase the degree of fiber alignment, so that

mimics the natural ECM orientation in tumors. By modulating the cell number encapsulated in

gels, as well as the gel height, we can alter the oxygen diffusion rate and generate hypoxic

regions within this in vitro model. To analyze sarcoma cell behavior, we culture individual

sarcoma cells and small mice tumor grafts in hypoxic, aligned collagen gels and compare with

their randomly oriented counterparts in atmospheric conditions. The topographical cues of

ECM, such as collagen architecture, influence the cancer cell proliferation and motility through

altering cell-fiber interaction. From this we further study collagen modifiers/cross-linkers as

well as focal adhesion kinase, as they influence cancer proliferation in the oxygen-extracellular

matrix (ECM) tumor microenvironment. We show corresponding factors that correlate with the

proliferative response of sarcoma cells in this truly physiologically mimicking platform.