Characterizing Hypoxia-induced Alterations in ECM Integrity of Solid Tumors In Vivo Using MRI and Fluorescent Microscopy
Pathak A, Artemov D, Bhujwalla Z, Raman V
Johns Hopkins University School of Medicine
Tumor microenvironmental factors are critical determinants in the phenotypic traits of cancer. Of these, hypoxia is known to induce drug/radiation resistance, and select for a more aggressive phenotype. However, the relationship between hypoxia, the resultant ECM remodeling and macromolecular transport in vivo remains largely unexplored. Hypoxia is known to induce collagen deposition, and induce upregulation of various matrix metalloproteinases (MMPs) that remodel the ECM and affect the movement of macromolecules. Here for the first time we have related the macromolecular movement through the ECM to tumor hypoxia, using optical molecular imaging of tumor hypoxia in conjunction with novel MRI analyses.