In Cancer Research this week, a team led by researchers at Laval University in Canada describe the molecular signature found in the lung tissue of smokers. The team carried out genome-wide gene expression profiling on normal lung tissue from 853 lung cancer patients and compared gene expression between current and never smokers, as well as changes in gene expression over time in the lung tissue of former smokers. "A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set," the team says. "A substantial number of smoking-induced genes also were validated in two replication sets, and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets." Further, the team also found that some genes showed almost no reversibility in expression once altered by smoking. "Smoking deregulates many genes, many of which reverse to normal following smoking cessation," the authors add. "However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers."
Also in Cancer Research this week, researchers in South Korea and the US report that MET signaling regulates glioblastoma stem cells. The team identified a distinct fraction of cells expressing a high level of MET in samples of human primary glioblastoma tissues. These cells were highly clonogenic, tumorigenic, and resistant to radiation. "Inhibition of MET signaling in [glioblastoma stem cells] disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs," the authors write. "Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target."
Finally in Cancer Research this week, researchers in the US and Germany report that the ganglioside GD3 suppresses innate immune response in patients with ovarian cancer. The team isolated GD3 from the polar lipid fraction of ovarian cancer-associated ascites and determined that it inhibits the activation of natural killer T-cells. "Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells," the authors write. "Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells."