As tumors grow, some regions lack a blood supply adequate to maintain good levels of oxygen, that is some regions become hypoxic. This is a hallmark of malignant tumors and has been suggested, but not experimentally proven, to promote tumor progression.
However, Paolo Michieli and colleagues, at the University of Turin Medical School, Italy, have now developed xenograft models to examine how human lung tumors without regions of hypoxia develop and found that tumors rely on hypoxia to promote their own expansion.
In the study, human lung cancer cells were engineered to express the protein myoglobin, which specializes in oxygen transport, storage, and buffering. When these cells were injected into mice, the tumors that developed exhibited no regions of hypoxia, and this was associated with both markedly reduced tumor growth and an inability to metastasize to secondary locations.
Further analysis confirmed that the effects were mainly a result of decreased tumor hypoxia, leading the authors to conclude that hypoxia seems to be a key factor driving tumor progression.
In an accompanying commentary, Ulrich Flφgel and Chi Dang, highlight the importance of these data and discus other ways in which myoglobin might affect tumor progression.
The research is published in the March 23, 2009, issue of the Journal of Clinical Investigation.
- Maria Galluzzo, Selma Pennacchietti, Stefania Rosano, Paolo M. Comoglio and Paolo Michieli. Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI36579
- Ulrich Flφgel, Chi V. Dang. Myoglobin tames tumor growth and spread. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38796
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