Article

Lung cancer signatures in plasma based on proteome profiling of mouse tumor models.

Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancer cell (Impact Factor: 23.89). 09/2011; 20(3):289-99. DOI: 10.1016/j.ccr.2011.08.007
Source: PubMed

ABSTRACT We investigated the potential of in-depth quantitative proteomics to reveal plasma protein signatures that reflect lung tumor biology. We compared plasma protein profiles of four mouse models of lung cancer with profiles of models of pancreatic, ovarian, colon, prostate, and breast cancer and two models of inflammation. A protein signature for Titf1/Nkx2-1, a known lineage-survival oncogene in lung cancer, was found in plasmas of mouse models of lung adenocarcinoma. An EGFR signature was found in plasma of an EGFR mutant model, and a distinct plasma signature related to neuroendocrine development was uncovered in the small-cell lung cancer model. We demonstrate relevance to human lung cancer of the protein signatures identified on the basis of mouse models.

0 Followers
 · 
244 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory diseases are highly prevalent and affect humankind worldwide causing extensive morbidity and mortality with the environment playing an important role. Given the complex structure of the airways sophisticated tools are required for early diagnosis; initial symptoms are non-specificand the clinical diagnosis is made frequently late.Over the last few years, proteomics has made a high technological progress in mass spectrometry-based protein identification, and has allowed gaining new insides into disease mechanisms and identifying potential novel therapeutic targets. This review will highlight the contributions of proteomics towards the understanding of the respiratory proteome listing potential biomarkers, and its potential application to the clinic. We also outline the contributions of proteomics to creating a personalized approach in respiratory medicine.
    Journal of Proteome Research 11/2014; 14(1). DOI:10.1021/pr500935s · 5.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: According to the China tumor registry 2013 annual report , breast cancer, lung cancer, and ovarian cancer are three common cancers in China nowadays, with high mortality due to the absence of early diagnosis technology. However, proteomics has been widespreadly implanted into every field of life science and medicine as an important part of post-genomics era research. The development of theory and technology in proteomics has provided new ideas and research fields for cancer research. Proteomics can be used not only for elucidating the mechanisms of carcinogenesis focussing on whole proteins of the tissue or cell, but also seeking the biomarkers for diagnosis and therapy of cancer. In this review, we introduce proteomics principles, covering current technology used in exploring early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer.
    Asian Pacific journal of cancer prevention: APJCP 11/2014; 15(20):8529-8538. DOI:10.7314/APJCP.2014.15.20.8529 · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular vesicles (EVs) are small nanometre-sized vesicles that are circulating in blood. They are released by multiple cells, including tumour cells. We hypothesized that circulating EVs contain protein kinases that may be assessed as biomarkers during treatment with tyrosine kinase inhibitors. EVs released by U87 glioma cells, H3255 and H1650 non-small-cell lung cancer (NSCLC) cells were profiled by tandem mass spectrometry. Total AKT/protein kinase B and extracellular signal regulated kinase 1/2 (ERK1/2) levels as well as their relative phosphorylation were measured by western blot in isogenic U87 cells with or without mutant epidermal growth factor receptor (EGFRvIII) and their corresponding EVs. To assess biomarker potential, plasma samples from 24 healthy volunteers and 42 patients with cancer were used. In total, 130 different protein kinases were found to be released in EVs including multiple drug targets, such as mammalian target of rapamycin (mTOR), AKT, ERK1/2, AXL and EGFR. Overexpression of EGFRvIII in U87 cells results in increased phosphorylation of EGFR, AKT and ERK1/2 in cells and EVs, whereas a decreased phosphorylation was noted upon treatment with the EGFR inhibitor erlotinib. EV samples derived from patients with cancer contained significantly more protein (p=0.0067) compared to healthy donors. Phosphorylation of AKT and ERK1/2 in plasma EVs from both healthy donors and patients with cancer was relatively low compared to levels in cancer cells. Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005). Phosphorylation of protein kinases in EVs reflects their phosphorylation in tumour cells. Total AKT protein levels may allow monitoring of kinase inhibitor responses in patients with cancer.
    12/2014; 3:25657. DOI:10.3402/jev.v3.25657

Full-text (2 Sources)

Download
58 Downloads
Available from
May 16, 2014