Hypoxic Environments Disrupt Collagen I Fibers and Macromolecular Transport

Samata Kakkad¹, Marie-France Penet¹, Meiyappan Solaiyappan¹, Arvind Pathak¹, 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 fiber formation. Hypoxic environments in tumors may lead to abnormal collagen deposits either by cancer cells or by fibroblasts within the tumor stroma. In normal 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 was to understand the role of hypoxia in modifying macromolecular fluid transport using MRI, and collagen fiber distribution using second harmonic generation microscopy.