Location, location, location-makes all the difference for hypoxia in lung tumors

Abstract

Hypoxia is a clinically important component of the tumor microenvironment because it adversely affects progression, metastasis, response to chemoradiation therapy, and overall patient survival. Here, we describe how different animal tumor models of lung cancer can yield surprisingly different hypoxic profiles.

Fig. 1

A, different tumor models used in the study by Graves et al. From left to right: A549 human lung adenocarcinoma cells grown heterotopically in the flank of a nude mouse; A549 cells implanted orthotopically in the lung of the mouse; spontaneous mutant K-Ras– or Myc-induced lung tumors and human lung cancers. The relative areas of hypoxia are depicted in red with the more intense color representing more hypoxic tumors. B, different methods used to detect and measure hypoxia in solid tumors. Left: mice were injected with the hypoxia-sensitive marker pimonidazole (PIMO) whose adducts formed under hypoxia can be detected by immunohistochemistry. Also, mice were injected with the radioactive nitroimidazole tracer FAZA, which accumulates in hypoxic cells and is detected by microPET. Right: diagram depicting direct measurement of tumor oxygenation by repeated sampling of tumor pO₂ with the Eppendorf electrode. The results are usually depicted as a series of bars representing the frequency of readings plotted against specific pO₂ values (mm Hg).