Combo of Tumor Inhibitor, Immune System Modulator Makes NSCLC Resistant

TIMP-1, IL-6 Seem To Team Up To Fend Off Tx drugs

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