Clinical Cancer Research Holland
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Clinical Cancer Research 14, 5494-5502, September 1, 2008. doi: 10.1158/1078-0432.CCR-08-0233
© 2008 American Association for Cancer Research

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Cancer Therapy: Preclinical

TMTP1, a Novel Tumor-Homing Peptide Specifically Targeting Metastasis

Wanhua Yang, Danfeng Luo, Shixuan Wang, Rui Wang, Rui Chen, Yan Liu, Tao Zhu, Xiangyi Ma, Ronghua Liu, Gang Xu, Li Meng, Yunping Lu, Jianfeng Zhou and Ding Ma

Authors' Affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China

Requests for reprints: Ding Ma or Jianfeng Zhou, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubai 430030, People's Republic of China. Phone: 86-27-83662779; Fax: 86-27-83662681; E-mail: dma{at}tjh.tjmu.edu.cn.

Purpose: Tumor metastasis continues to be the major obstacle to cancer therapy and the leading cause of cancer-related death. Methods used to detect metastasis, especially occult metastases, have received a great deal attention. In this study, a novel selective peptide was assessed for its specific binding to metastasis.

Methods: The FliTrx bacterial peptide display system, an alternative to phage peptide display, was used to identify a 5-amino acid peptide termed TMTP1 (NVVRQ), which binds to the highly metastatic prostate cancer cell line PC-3M-1E8. The synthetic TMTP1 was tested in vitro for its binding specificity and affinity to highly metastatic cancer cells. The tumor targeting assays were done in vivo by i.v. injection of FITC-conjugated TMTP1 into tumor-bearing mice.

Results: TMTP1 specifically bound to a series of highly metastatic tumor cells, including prostate cancer PC-3M-1E8, breast cancer MDA-MB-435S, lung cancer PG-BE1, and gastric cancer MKN-45sci, in vitro and in vivo but not to the poorly metastatic or nonmetastatic cell line, including prostate cancer PC-3M-2B4, breast cancer MCF-7, lung cancer PG-LH7, or murine fibroblast cell NIH/3T3. FITC-TMTP1 strongly and specifically targeted the metastasis foci in tumor-bearing mice 24 h after i.v. peptide injection. Moreover, the occult metastases were specifically detected by FITC-TMTP1.

Conclusion: Our results suggest that TMTP1 is a potential strategy for the development of new diagnostic tracers or alternative anticancer agents for tumor metastasis.







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Copyright © 2008 by the American Association for Cancer Research.