Hamilton Gerhard, Rath Barbara
Department of Surgery, Medical University of Vienna, 1090, Vienna, Austria.
Ludwig Boltzmann Cluster of Translational Oncology, 1090, Vienna, Austria.
Wien Med Wochenschr. 2015 Oct;165(19-20):379-86. doi: 10.1007/s10354-015-0381-6. Epub 2015 Aug 20.
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.
小细胞肺癌（SCLC）占所有肺部肿瘤的15%，是一种侵袭性神经内分泌恶性肿瘤，生存率较低。这种癌症在吸烟者中高度流行，其特征是p53和视网膜母细胞瘤失活。首次对SCLC患者的循环肿瘤细胞（CTC）进行体外扩增，使得对肿瘤播散的细胞生物学研究成为可能。在建议的CTC SCLC模型中，原发性肿瘤吸引并诱导促肿瘤和免疫抑制巨噬细胞，这些巨噬细胞反过来促使CTC扩散并产生远处病变。与慢性阻塞性肺疾病（COPD）相关的既往炎症过程似乎会增强肿瘤相关巨噬细胞（TAM）的后续活性。SCLC CTC中信号转导和转录激活因子3（STAT3）的激活以及几丁质酶-3样1/YKL-40的表达似乎与耐药性有关。总之，炎症相关的侵袭性和化疗耐药性CTC的产生很可能解释了SCLC的特征，即早期播散和化疗迅速失效。
