Tumor Cell Heterogeneity in Small Cell Lung Cancer (SCLC): Phenotypical and Functional Differences Associated with Epithelial-Mesenchymal Transition (EMT) and DNA Methylation Changes

• DOI: 10.1371/journal.pone.0100249
• Publication Date: 2014-06-24T20:31:21Z
• Authors: Alexander Krohn; Theresa Ahrens; Arzu Yalcin; Till Plönes; Julius Wehrle; Sanaz Taromi; Stefan Wollner; Marie Follo; Thomas Brabletz; Sendurai A. Mani; Rainer Claus; Björn Hackanson; Meike Burger
• Keywords: 0301 basic medicine; Epithelial-Mesenchymal Transition; Lung Neoplasms; Science; 610; Gene Expression; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Vimentin; Genetic Association Studies; ddc:610; Q; R; DNA Methylation; Cadherins; Small Cell Lung Carcinoma; Matrix Metalloproteinases; 3. Good health; Drug Resistance, Neoplasm; Proteolysis; Medicine; Extracellular Space; Biomarkers; Research Article

Small Cell Lung Cancer (SCLC) is a specific subtype of lung cancer presenting as highly metastatic disease with extremely poor prognosis. Despite responding initially well to chemo- or radiotherapy, SCLC almost invariably relapses and develops resistance chemotherapy. This suspected be related tumor cell subpopulations different characteristics resembling stem cells. Epithelial-Mesenchymal Transition (EMT) known play key role in processes developing drug resistance. also true for NSCLC, but there very little information on EMT so far. SCLC, contrast NSCLC lines, grow mainly floating clusters minor part adherent We compared these morphologically lines epigenetic features, detecting significant differences the high levels mesenchymal markers such Vimentin Fibronectin low epithelial like E-cadherin Zona Occludens 1. In addition, expression EMT-related transcription factors Snail/Snai1, Slug/Snai2, Zeb1, DNA methylation patterns hallmark genes, functional responses migration, invasion, matrix metalloproteases secretion, chemotherapeutic treatment all differed significantly between sublines. phenotypic variability might reflect heterogeneity during metastasis vivo, accompanied by development refractory relapse. propose that regulation plays phenotypical changes cells therefore provide new options patients.