@Article{ecn.2007.0087,
AUTHOR = {Evemie Schutyser, Yingjun Su, Yingchun Yu, Mieke Gouwy, Snjezana Zaja-Milatovic, Jo Van Damme, Ann Richmond},
TITLE = {Hypoxia enhances CXCR4 expression in human microvascular endothelial cells and human melanoma cells},
JOURNAL = {European Cytokine Network},
VOLUME = {18},
YEAR = {2007},
NUMBER = {2},
PAGES = {59--70},
URL = {http://www.techscience.com/ECN/v18n2/65996},
ISSN = {1952-4005},
ABSTRACT = {The influence of environmental factors (cytokines, matrix components, serum factors and O<sub>2</sub> level)
on expression of receptors for angiogenic versus angiostatic CXC chemokines in human microvascular endothelial
cells has not been extensively investigated. Our semi-quantitative RT-PCR analysis demonstrated that TNF-α and
IFN-γ repressed CXCR4 mRNA levels in immortalized human microvascular endothelial HMEC-1 cells after 4 h,
whereas only TNF-α displayed inhibitory activity in primary human microvascular endothelial cells (HMVEC).
CXCR4 mRNA expression was not affected by VEGF, GM-CSF, IL-1β or various basal membrane matrix
components, but was significantly up-regulated after serum starvation and/or hypoxic treatment of the
microvascular endothelial cells. The alternative CXCL12 receptor, CXCR7/RDC1, was also up-regulated by
hypoxia in HMEC-1 cells, although less consistently than CXCR4. Furthermore, hypoxia and serum starvation
were required for cell surface display of CXCR4 and CXCL12 induction of ERK activation in HMEC-1 cells. In
contrast, CXCR2 and CXCR3 mRNA levels remained, respectively, low and undetectable under all the conditions
tested, and surface expression of CXCR2, CXCR3 and CXCR7 on the HMEC- 1 cells could not be demonstrated
by FACS. In the human SK-MEL-5 melanoma cell line, CXCR4 mRNA expression was also increased under
hypoxic conditions, whereas CXCR2 mRNA levels remained low and levels of CXCR3 and CXCR7 were
undetectable. However, immunohistochemical staining of human metastatic melanoma sections demonstrated that
CXCR2, CXCR3, CXCR4 and CXCR7 are expressed on tumor cells and, to a lesser extent, on endothelial cells.
These results demonstrate that the tumor microenvironment regulates chemokine receptor expression through
both cytokine and oxygen levels.},
DOI = {10.1684/ecn.2007.0087}
}