title: mir-1-mediated paracrine effect of cancer-associated fibroblasts on lung cancer cell proliferation and chemoresistance.
abstract: Lung cancer is the leading cause of cancer-related mortality in humans worldwide. Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80% of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) have been found to exist in a large number of NSCLCs. CAFs have been proven to promote tumor progression, metastasis and resistance to therapy through paracrine effects in most solid tumors. In the present study, firstly we isolated CAFs from patient tissues and demonstrated that they promoted cell proliferation and chemoresistance to cisplatin in the lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA and quantative PCR, we found that a higher amount of stromal cell-derived factor 1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation and drug resistance via the CXCR4-mediated signaling pathway which involved NF-κB and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1 in the CAFs was negatively regulated by microRNA mir-1 through microRNA overexpression and quantitative PCR. Overall, our data provide one explanation for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest CAFs as a potential therapeutic target in tumor treatment.
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of the University of South China, Hengyang, Hunan 421000, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xiang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology; D000072645:Cancer-Associated Fibroblasts / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D051020:bcl-X Protein; D002945:Cisplatin