A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma.

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.

• Authors: Wenxia Meng, Yun Wu, Xin He, Chuanxia Liu, Qinghong Gao, Lin Ge, Lanyan Wu, Ying Liu, Yiqing Guo, Xiaoyu Li, Yurong Liu, Sixiu Chen, Xiangli Kong, Zhi Liang, Hongmei Zhou
• Journal: Cancer research (Cancer Res) Vol. 74 Issue 8 Pg. 2306-15 (Apr 15 2014) ISSN: 1538-7445 [Electronic] United States
• PMID: 24556718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 AACR.

Chemical References

• Receptors, Transforming Growth Factor beta

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Communication (physiology)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Disease Progression
• Epithelial-Mesenchymal Transition
• Female
• Fibroblasts (pathology)
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mouth Neoplasms (genetics, metabolism, pathology)
• Receptors, Transforming Growth Factor beta (genetics, metabolism)
• Squamous Cell Carcinoma of Head and Neck
• Stromal Cells (metabolism, pathology)
• Transfection