Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice.

@article{citeulike:2800327, abstract = {PRL-1 (phosphatase of regenerating liver-1), PRL-2, and PRL-3 are protein tyrosine phosphatases with a C-terminal prenylation motif that are localized to the inner leaflet of the plasma membrane and early endosomes. A variety of metastatic PRL-overexpressing cancers have been reported. Therefore, the three PRL-phosphatases represent an intriguing group of proteins being validated as biomarkers and therapeutic targets in cancer. Targeting intracellular PRLs to prevent cancer metastasis by exogenous reagents is a challenging task. In an attempt to destroy PRL-overexpressing cancer cells with their respective PRL-antibodies, we generated an animal model that allows rapid formation of aggressive metastatic tumors caused by inoculation of PRL-1- or PRL-3-expressing cells. Surprisingly, mice treated with PRL-1 or PRL-3 mAbs show inhibition of tumor formation by approximately 90\% compared to untreated mice. Here we provide the first examples that PRL-1 and PRL-3 mAbs are able to target their respective phosphatases specifically and efficiently despite their intracellular localization to block cancer metastasis in experimental animals. Furthermore, we also demonstrate that PRL-1 mAb specifically blocks the formation of metastatic tumors formed by PRL-1- (but not PRL-3-) expressing cells; while PRL-3 mAb specifically blocks tumor formation of PRL-3- (but not PRL-1-) expressing cells. More importantly, we show that metastatic tumor formation by A2780 human ovarian cancer cells that express endogenous PRL-3 is dramatically blocked by PRL-3 antibodies. In contrast, the PRL-3 antibody treatment has no effect on tumor formation of CT26 mouse colon cancer cells which do not naturally express PRL-3 protein. Our data provide hope for the treatment of PRL-expressing cancers and will prompt a reevaluation of a wide spectrum of intracellular oncoproteins as possible targets with mAbs for anticancer therapy.}, address = {Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.}, author = {Guo, Ke and Li, Jie and Tang, Jing P. and Tan, Cheng Peow P. and Wang, Haihe and Zeng, Qi }, citeulike-article-id = {2800327}, issn = {1555-8576}, journal = {Cancer biology \& therapy}, keywords = {antibody, intracellular, phosphatase, target}, month = {February}, number = {5}, posted-at = {2008-05-15 01:00:39}, priority = {5}, title = {Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18364570}, volume = {7}, year = {2008} }

TY - JOUR ID - citeulike:2800327 L3 - citeulike-article-id:2800327 TI - Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice. JF - Cancer biology & therapy VL - 7 IS - 5 AD - Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. SN - 1555-8576 N2 - PRL-1 (phosphatase of regenerating liver-1), PRL-2, and PRL-3 are protein tyrosine phosphatases with a C-terminal prenylation motif that are localized to the inner leaflet of the plasma membrane and early endosomes. A variety of metastatic PRL-overexpressing cancers have been reported. Therefore, the three PRL-phosphatases represent an intriguing group of proteins being validated as biomarkers and therapeutic targets in cancer. Targeting intracellular PRLs to prevent cancer metastasis by exogenous reagents is a challenging task. In an attempt to destroy PRL-overexpressing cancer cells with their respective PRL-antibodies, we generated an animal model that allows rapid formation of aggressive metastatic tumors caused by inoculation of PRL-1- or PRL-3-expressing cells. Surprisingly, mice treated with PRL-1 or PRL-3 mAbs show inhibition of tumor formation by approximately 90% compared to untreated mice. Here we provide the first examples that PRL-1 and PRL-3 mAbs are able to target their respective phosphatases specifically and efficiently despite their intracellular localization to block cancer metastasis in experimental animals. Furthermore, we also demonstrate that PRL-1 mAb specifically blocks the formation of metastatic tumors formed by PRL-1- (but not PRL-3-) expressing cells; while PRL-3 mAb specifically blocks tumor formation of PRL-3- (but not PRL-1-) expressing cells. More importantly, we show that metastatic tumor formation by A2780 human ovarian cancer cells that express endogenous PRL-3 is dramatically blocked by PRL-3 antibodies. In contrast, the PRL-3 antibody treatment has no effect on tumor formation of CT26 mouse colon cancer cells which do not naturally express PRL-3 protein. Our data provide hope for the treatment of PRL-expressing cancers and will prompt a reevaluation of a wide spectrum of intracellular oncoproteins as possible targets with mAbs for anticancer therapy. KW - antibody KW - intracellular KW - phosphatase KW - target AU - Guo, Ke AU - Li, Jie AU - Tang, Jing AU - Tan, Cheng Peow AU - Wang, Haihe AU - Zeng, Qi PY - 2008/02/20/ UR - http://view.ncbi.nlm.nih.gov/pubmed/18364570 ER -