Scientists at the Medical College of Georgia and the Georgia Cancer Center at Augusta University, have identified one way lung cancer cells circumvent chemotherapy, according to a report in BioSpace.
Researchers were able to unwind the mechanisms of action of a tumor inhibitor, TIMP-1, which at high levels in lung cancer, indicates a poor prognosis.
TIMP-1 triggers the expression of an immune system modulator called IL-6, which is associated with treatment resistance. The study found that when lung cancer is treated with chemotherapy, the levels of both TIMP-1 and IL-6 increase.
Researchers, led by Mumtaz Rojiani, an Augusta University cancer biologist, studied whether TIMP-1 allowed cancer cells to avoid a chemotherapy drug. They found an increase in IL-6, which can modulate inflammation, appears to regulate TIMP-1 in some cancers. But in lung cancer, specifically non-small cell lung cancer, TIMP-1 was regulating IL-6.
“We have shown for the first time that if TIMP-1 goes up, IL-6 goes up and if TIMP-1 goes down, IL-6 goes down,” said Amyn Rojiani, chair of the MCG Department of Pathology and co-author of the study published in the journal Cancers. “And we have shown it in multiple different ways.”
The scientists evaluated non-small cell lung cancer cells and human cells that had TIMP-1 removed. They treated the cells without TIMP-1 with common chemotherapeutic drugs, gemcitabine and cisplatin. The result was IL-6 production decreased and cell death went up.
When TIMP-1 was added, IL-6 levels went up and cell survival increased. But the surviving cancer cells had higher levels of TIMP-1 and IL-6, making them even more treatment-resistant that the original cancer cells.
An analysis of the National Cancer Institute’s Cancer Genome Atlas database found that patients with NSCLC with low TIMP-1 and IL-6 levels had higher survival rates, according to Wei Xiao, MCG postdoctoral fellow and the study’s first author. When TIMP-1 and IL6 were elevated, however, survival was found to be significantly worse than when TIMP-1 levels alone were elevated.
“The two-gene signature became very important,” Mumtaz Rojiani said.
Source: Biospace, September 24