Tissue Proteomics Reveals Differential and Compartment-Specific Expression of the Homologs Transgelin and Transgelin-2 in Lung Adenocarcinoma and Its Stroma

• DOI: 10.1021/pr900705r
• Publication Date: 2009-10-22T20:01:51Z
• Authors: Jung-hyun Rho; Michael H. A. Roehrl; Julia Y. Wang
• Keywords: Compartment (ship)

Discovery of tissue-specific biomarkers for human cancer is crucial early diagnosis and molecular understanding the disease. To overcome limitations posed by large dynamic concentration range compositional complexity tissue biomacromolecules, we applied heparin affinity fractionation proteomic enrichment. Comparing proteomes five paired samples normal lung pulmonary adenocarcinoma 2-D difference gel electrophoresis, 14 spots were found to be differentially expressed. From these candidate spots, three proteins overexpressed in identified mass spectrometry as transgelin (TAGLN, SM22-alpha, WS3-10), transgelin-2 (TAGLN2), cyclophilin A (PPIA). Quantitative RT-PCR indicated that both TAGLN2 PPIA upregulated at transcriptional level. Differential protein expression levels validated Western blot analysis using an independent set 10 samples. Using immunohistochemistry on sections, discovered overexpression TAGLN was strictly localized tumor-induced reactive myofibroblastic stromal compartment, whereas exclusively neoplastic glandular compartment. Thus, highly homologous pair displayed mutually exclusive, compartment-specific cell type regulation tumor stroma vs epithelial cells. Our data further suggest may a marker active remodeling vicinity invasive carcinomas. It shed light mechanisms tumor-stroma interaction could useful diagnosis, treatment guidance, response monitoring.