Characterization of Macromolecular Transport in Hypoxic Tumor Environments with Disrupted Collagen I Fibers

Samata M. Kakkad¹, Marie-France Penet¹, Arvind Pathak¹, Meiyappan Solaiyappan¹, Venu Raman¹, Kristine Glunde¹, Zaver M. Bhujwalla¹

Solid tumors are characterized by hypoxic environments. Hypoxia stimulates the gene expression of a cluster of hydroxylases used for collagen I fiber formation. Hypoxic environments in tumors may lead to abnormal collagen deposits either by cancer cells or by fibroblasts within the tumor stroma. In healthy tissue, collagen fibers direct interstitial fluid into lymphatic channels. In tumors, these fibers may not be structured for efficient flow of fluid, especially in hypoxic areas. Our purpose is to understand the role of hypoxia in modifying macromolecular fluid transport using MRI, and collagen I fiber distribution using second harmonic generation microscopy.