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HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s
Li, Ling Tang, Wenhua Wu, Xiaoqing Karnak, David Meng, Xiaojie Thompson, Rachel Hao, Xinbao Li, Yongmin Qiao, Xiaotan T. Lin, Jiayuh
Li, Ling
Tang, Wenhua
Wu, Xiaoqing
Karnak, David
Meng, Xiaojie
Thompson, Rachel
Hao, Xinbao
Li, Yongmin
Qiao, Xiaotan T.
Lin, Jiayuh
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Abstract
Purpose
STAT3 plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 is failure in clinic. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo.
Experimental Design
The expression of HAb18G/CD147, pSTAT3 and CD44s were determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 was assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot, immunofluorescence staining, immunoprecipitation, and in vivo tumor formationusing loss or gain-of-function strategies.
Results
Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. CyPA, a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147 dependent mechanisms. HAb18G/CD147 was associated and co-localized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high co-expression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer.
Conclusions
We identified HAb18G/CD147 as a novel upstream activator of STAT3 via interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies.
Description
Date
2014-12-15
Journal Title
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Volume Title
Publisher
American Association for Cancer Research
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Keywords
Pancreatic cancer, HAb18G/CD147, CD44, STAT3, Tumor development
Citation
Li, L., W. Tang, X. Wu, D. Karnak, X. Meng, R. Thompson, X. Hao, Y. Li, X. T. Qiao, J. Lin, J. Fuchs, D. M. Simeone, Z.-N. Chen, T. S. Lawrence, and L. Xu. "HAb18G/CD147 Promotes PSTAT3-Mediated Pancreatic Cancer Development via CD44s." Clinical Cancer Research 19.24 (2013): 6703-715.