期刊
FRONTIERS IN PHARMACOLOGY
卷 4, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2013.00034
关键词
cyclooxygenase 2; inflammation and cancer; inflammation and hypoxia; COX-2 and HIF-1; COX-2 and LEF-1; invasion; metastasis; COX-2 inhibitors
资金
- NIH [P50 CA103175, P30 CA006973, R01 CA73850, R01 CA82337, R01 CA136576, R01 CA138515, R01 CA138264]
- NATIONAL CANCER INSTITUTE [R01CA082337, P50CA103175, R01CA138515, R01CA138264, R01CA073850, R01CA136576, P30CA006973] Funding Source: NIH RePORTER
The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade, and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes, several of which are mediated by COX-2, approach the complexities of a Gordian Knot. We review evidence from our studies and from literature suggesting that cyclooxygenase-2 (COX-2) biology presents a nodal point in cancer biology and an Achilles heel of COX-2-dependent tumors.
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