Protein expression suppressed spread of urothelial cancer to lungs

Said N. J Clin Invest. 2012;doi:10.1172/JCI61392.

  • HemOnc Today, April 10, 2012

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 protein expression.

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 fusion protein.

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 versican.

“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.

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