Oncotarget

Research Papers:

A targeted transforming growth factor-beta (TGF-β) blocker, TTB, inhibits tumor growth and metastasis

Changhua Zhou, Jing Li, Limin Lin, Rui Shu, Bin Dong, Donglin Cao, Qing Li _ and Zhong Wang

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Oncotarget. 2018; 9:23102-23113. https://doi.org/10.18632/oncotarget.24562

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Abstract

Changhua Zhou1,2,*, Jing Li1,2,*, Limin Lin1,2, Rui Shu3, Bin Dong4, Donglin Cao5, Qing Li1,2 and Zhong Wang1,2

1School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China

2Center for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, 510006, China

3Ying Rui Inc., Guangzhou, Guangdong, 510009, China

4School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510009, China

5Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China

*Co-first authors

Correspondence to:

Qing Li, email: [email protected]

Zhong Wang, email: [email protected]

Keywords: TGF-β; TGF-β inhibitors; cancer metastasis; receptor; RGD

Received: May 19, 2017    Accepted: July 13, 2017    Epub: February 24, 2018    Published: May 01, 2018

ABSTRACT

Transforming growth factor beta (TGF-β) promotes cancer growth in late stage cancers. To inhibit the TGF-β pathway, we investigated a tumor-targeting TGF-β receptor blocker, TTB, and its role in tumor progress. The targeted TTB comprised of the extracellular domain of the TGF-β receptor II, the endoglin domain of TGF-β receptor III, and the human immuno-globin IgG1 constant fragment (Fc). To enhance tumor microenvironment targeting, a RGD peptide was fused at the N-terminal of TTB. The targeted TTB exhibited potent TGF-β neutralization activities, and inhibited cancer cell migration and invasion as well as colony formation. In xenograft models, the TTB had potent tumor inhibition activities. The TTB also attenuated the TGF-β1-induced Smad2 phosphorylation and epithelial to mesenchymal transformation (EMT), and suppressed breast cancer metastasis. Thus, the TTB is an effective TGF-β blocker with a potential for blocking excessive TGF-β induced pathogenesis in vivo.


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