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Clinical Cancer Research Vol. 11, 2195-2204, March 2005
© 2005 American Association for Cancer Research


Imaging, Diagnosis, Prognosis

Generation of PRL-3- and PRL-1-Specific Monoclonal Antibodies as Potential Diagnostic Markers for Cancer Metastases

Jie Li1, Ke Guo1, Vicki Wei Chyi Koh1, Jing Ping Tang1, Bin Qi Gan1, Hong Shi1, Hui Xiang Li2 and Qi Zeng1

1 Institute of Molecular and Cell Biology, Proteos, Singapore and 2 Department of Pathology, Henan Medical University, Henan, Zheng Zhou, China

Requests for reprints: Qi Zeng, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673. Phone: 65-6586-9664; Fax: 65-6779-1117; E-mail: mcbzengq{at}imcb.a-star.edu.sg.

Purpose: The PRL-3 mRNA is consistently elevated in metastatic samples derived from colorectal cancers. We sought to generate a specific PRL-3 monoclonal antibody (mAb) that might serve as a potential diagnostic marker for colorectal cancer metastasis.

Experimental Design: PRL-3 is one of three members (PRL-1, PRL-2, and PRL-3) in a unique protein-tyrosine phosphatase family. Because the three PRLs are 76% to 87% identical in their amino acid sequences, it poses a great challenge to obtain mAbs that are specific for respective phosphatase of regenerating liver (PRL) but not for the other two in the family. We screened over 1,400 hybridoma clones to generate mAbs specific to each PRL member.

Results: We obtained two hybridoma clones specifically against PRL-3 and another two clones specifically against PRL-1. These antibodies had been evaluated by several critical tests to show their own specificities and applications. Most importantly, the PRL-3 mAbs were assessed on 282 human colorectal tissue samples (121 normal, 17 adenomas, and 144 adenocarcinomas). PRL-3 protein was detected in 11% of adenocarcinoma samples. The PRL-3- and PRL-1-specific mAbs were further examined on 204 human multiple cancer tissues. The differential expressions of PRL-3 and PRL-1 confirmed the mAbs' specificity.

Conclusions: Using several approaches, we show that PRL-3- or PRL-1-specific mAbs react only to their respective antigen. The expression of PRL-3 in >10% of primary colorectal cancer samples indicates that PRL-3 may prime the metastatic process. These mAbs will be useful as markers in clinical diagnosis for assessing tumor aggressiveness.

Key Words: Phosphatase Inhibitors • Metastatic Markers • Drug Therapy




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2005 by the American Association for Cancer Research.