The role of nitric oxide in modulating the hypoxic tumor response

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Tumor cells respond to hypoxia by activating hypoxia-inducible factor 1 (HIF-1), which controls metabolic adaptation, angiogenesis, and metastasis. Invading macrophages from the stroma of the host communicate with the tumor by releasing nitric oxide. We have found that nitric oxide can modulate the cellular oxygen-sensing process that controls HIF-1–dependent hypoxic gene activation. Understanding the mechanisms underlying this modulation would provide a deeper insight into the communication between tumor and host and would provide the basis for targeting the mechanisms by which tumor cells survive hypoxia and spread.