Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis.

ABSTRACT: As a tumor grows, it requires increased amounts of oxygen. However, the tumor blood vessels that form to meet this demand are functionally impaired, leading to regions of hypoxia within the tumor. Such hypoxia is one of the hallmarks of malignancy and is thought to promote a number of tumorigenic properties. Here, we sought to determine how tumors without hypoxia would progress by engineering A549 human lung carcinoma cells to ectopically express myoglobin (Mb), a multifunctional heme protein that specializes in oxygen transport, storage, and buffering. Mb expression prevented the hypoxic response in vitro and delayed tumor engraftment and reduced tumor growth following xenotransplantation into mice. Experimental tumors expressing Mb displayed reduced or no hypoxia, minimal HIF-1alpha leve

SUBMITTER: Galluzzo M 

PROVIDER: S-EPMC2662552 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature