Smoking, inflammation and small cell lung cancer: recent developments.
Small cell lung cancer (SCLC) accounts for 15 % of all lung tumors and represents an invasive neuroendocrine malignancy with poor survival rates. This cancer is highly prevalent in smokers and characterized by inactivation of p53 and retinoblastoma. First in vitro expansion of circulating tumor cells (CTCs) of SCLC patients allowed for investigation of the cell biology of tumor dissemination. In the suggested CTC SCLC model, the primary tumor attracts and educates tumor-promoting and immunosuppressive macrophages which in turn arm CTCs to spread and generate distal lesions. Preexisting inflammatory processes associated with chronic obstructive pulmonary disease (COPD) seem to potentiate the subsequent activity of tumor-associated macrophages (TAM). Activation of signal transducer and activator of transcription 3 (STAT3) and expression of chitinase-3-like 1/YKL-40 in SCLC CTCs seems to be associated with drug resistance. In conclusion, inflammation-associated generation of invasive and chemoresistant CTCs most likely explains the characteristic features of SCLC, namely early dissemination and rapid failure of chemotherapy.
Department of Surgery, Medical University of Vienna, 1090, Vienna, Austria. gerhard.hamilton@meduniwien.ac.at.|Ludwig Boltzmann Cluster of Translational Oncology, 1090, Vienna, Austria. gerhard.hamilton@meduniwien.ac.at.
Gerhard
G
Hamilton
Ludwig Boltzmann Cluster of Translational Oncology, 1090, Vienna, Austria.
Barbara
B
Rath
D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology* / Q000276:immunology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*; D016676:Macrophages, Alveolar / Q000276:immunology; D009361:Neoplasm Invasiveness / Q000276:immunology; D009360:Neoplastic Cells, Circulating / Q000276:immunology; D011014:Pneumonia / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000276:immunology
Circulating tumor cells; Drug resistance; Metastasis; Oncogene; Small cell lung cancer (SCLC); Smoking