1. A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma
- Author
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Yun Wu, Lanyan Wu, Yurong Liu, Zhi Liang, Hongmei Zhou, Xin He, Chuanxia Liu, Sixiu Chen, Wenxia Meng, Xiaoyu Li, Lin Ge, Qinghong Gao, Ying Liu, Yiqing Guo, and Xiangli Kong
- Subjects
Cancer Research ,Cell type ,Stromal cell ,Epithelial-Mesenchymal Transition ,Systems biology ,Tumor initiation ,Cell Communication ,Biology ,Bioinformatics ,Transfection ,Mice ,Stroma ,Cell Line, Tumor ,Carcinoma ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Mice, Inbred BALB C ,Squamous Cell Carcinoma of Head and Neck ,Fibroblasts ,medicine.disease ,Cell Transformation, Neoplastic ,Oncology ,Head and Neck Neoplasms ,Cancer cell ,Cancer research ,Carcinoma, Squamous Cell ,Disease Progression ,Female ,Mouth Neoplasms ,Stromal Cells ,Receptors, Transforming Growth Factor beta - Abstract
The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-β receptor III (TβRIII) is found as an epithelial–mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TβRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TβRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies. Cancer Res; 74(8); 2306–15. ©2014 AACR.
- Published
- 2014