Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression.
作者： Limo Chen , Xiaohui Yi , Sangeeta Goswami , Young-Ho Ahn , Jonathon D. Roybal
DOI: 10.1080/2162402X.2016.1234570
关键词: Immunotherapy 、 Metastasis 、 Tumor progression 、 Adenocarcinoma 、 Immunosuppression 、 T cell 、 Cancer research 、 Lung cancer 、 Immunology 、 Cancer cell 、 Biology
摘要: Cancer cells modulate the recruitment and function of inflammatory to create an immunosuppressive microenvironment that favors tumor growth metastasis. However, tumor-derived regulatory programs promote intratumoral immunosuppression remain poorly defined. Here, we show in a KrasLA1/+p53R172HΔg/+-based mouse model bone morphogenetic protein-4 (BMP4) augments expression T cell co-inhibitory receptor ligand PD-L1 mesenchymal subset lung cancer cells, leading profound CD8+ cell-mediated immunosuppression, producing We previously reported this BMP4 functions as pro-tumorigenic factor regulated by miR-200 via GATA4/6. Thus, BMP4-mediated is part larger miR-200-directed gene program tumors promotes progression, which could have important implications for treatment.
utsystem.edu参考文章(58)
David P Bartel, MicroRNAs: Genomics, Biogenesis, Mechanism, and Function Cell. ,vol. 116, pp. 281- 297 ,(2004) , 10.1016/S0092-8674(04)00045-5
Anne Richter, Lena Valdimarsdottir, Helga Eyja Hrafnkelsdottir, Johann Frimann Runarsson, Arna Run Omarsdottir, Dorien Ward-van Oostwaard, Christine Mummery, Gudrun Valdimarsdottir, BMP4 Promotes EMT and Mesodermal Commitment in Human Embryonic Stem Cells via SLUG and MSX2 Stem Cells. ,vol. 32, pp. 636- 648 ,(2014) , 10.1002/STEM.1592
Limo Chen, John V Heymach, F Xiao-Feng Qin, Don L Gibbons, None, The mutually regulatory loop of epithelial–mesenchymal transition and immunosuppression in cancer progression OncoImmunology. ,vol. 4, ,(2015) , 10.1080/2162402X.2014.1002731
Jeong Seon Kim, Jonathan M. Kurie, Young-Ho Ahn, BMP4 depletion by miR-200 inhibits tumorigenesis and metastasis of lung adenocarcinoma cells Molecular Cancer. ,vol. 14, pp. 173- 173 ,(2015) , 10.1186/S12943-015-0441-Y
Xin Ye, Robert A. Weinberg, Epithelial–Mesenchymal Plasticity: A Central Regulator of Cancer Progression Trends in Cell Biology. ,vol. 25, pp. 675- 686 ,(2015) , 10.1016/J.TCB.2015.07.012
Lisa M. Coussens, Zena Werb, Inflammation and cancer Nature. ,vol. 420, pp. 860- 867 ,(2002) , 10.1038/NATURE01322
Karin E. de Visser, Alexandra Eichten, Lisa M. Coussens, Paradoxical roles of the immune system during cancer development Nature Reviews Cancer. ,vol. 6, pp. 24- 37 ,(2006) , 10.1038/NRC1782
Michel DuPage, Ann F. Cheung, Claire Mazumdar, Monte M. Winslow, Roderick Bronson, Leah M. Schmidt, Denise Crowley, Jianzhu Chen, Tyler Jacks, Endogenous T Cell Responses to Antigens Expressed in Lung Adenocarcinomas Delay Malignant Tumor Progression Cancer Cell. ,vol. 19, pp. 72- 85 ,(2011) , 10.1016/J.CCR.2010.11.011
Philip A. Gregory, Andrew G. Bert, Emily L. Paterson, Simon C. Barry, Anna Tsykin, Gelareh Farshid, Mathew A. Vadas, Yeesim Khew-Goodall, Gregory J. Goodall, The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 Nature Cell Biology. ,vol. 10, pp. 593- 601 ,(2008) , 10.1038/NCB1722
Don L. Gibbons, Wei Lin, Chad J. Creighton, Shuling Zheng, Dror Berel, Yanan Yang, Maria Gabriela Raso, Diane D. Liu, Ignacio I. Wistuba, Guillermina Lozano, Jonathan M. Kurie, Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma PLoS ONE. ,vol. 4, pp. e5401- ,(2009) , 10.1371/JOURNAL.PONE.0005401