Said N. J Clin Invest. 2012;doi:10.1172/JCI61392.
Elevated expression of the RhoGDI2 protein suppressed
lung metastasis by reducing the expression of other proteins integral to cancer
proliferation and migration, according to study results published in The
Journal of Clinical Investigation.
Based on previous studies, which established that
reduced mRNA expression of the RhoGDI2 protein was associated with poor
prognosis in patients with urothelial cancer, researchers used a
transcriptional screen to verify the outcome of varying levels of RhoGDI2
Researchers used high-density oligonucleotide
microarrays to compare the gene expression of low RhoGDI2 protein with highly
metastatic UMUC3 cells transfected with a green fluorescent protein-RhoGDI2
According to the results of the study, elevated
expression of the RhoGDI2 protein reduced the expression of the protein
versican — cancer cells that produced more RhoGDI2, in turn produced less
“For a decade, we’ve known that the major
challenge of treating bladder cancer is treating or preventing the metastatic
form of the disease. This study represents an advance in the latter — by
preventing the spread of bladder cancer to the lungs, we could improve patient
survival,” researcher Dan Theodorescu, MD, PhD, director of the
University of Colorado Cancer Center, said in a press release.
Integral to cancer metastasis, versican expression
signals the release of macrophages from the body’s immune system. The
higher the level of versican expression, the greater the number of macrophages
released by the immune system, which has been observed to aid cancer cell
survival and promote the growth of cancer cells that have landed in distant
sites, such as the lung, promoting metastasis of the disease.
“We believe this study provides an important
contribution to the scientific literature by delineating for the first time a
new mechanism of metastasis suppression, namely that suppression of metastasis
is possible by altering the tumor microenvironment, including reducing the
presence macrophages,” Theodorescu said.
Disclosure: The researchers report funding
support from the NIH.