Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies.

Abstract

Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in development, poor prognosis malignancies and cancer stem cells, is also a major therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis. We show that CDH11 is increased early in breast cancer and ductal carcinoma in-situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basal-like breast tumors and decreased proliferation and colony formation of breast, glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib, which binds to CDH11, and other small molecules designed to bind CDH11 without inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells in vitro and in animals. These data suggest that CDH11 is important for malignant progression, and is a therapeutic target in arthritis and cancer with the potential for rapid clinical translation.

• Authors: Shahin Assefnia, Sivanesan Dakshanamurthy, Jaime M Guidry Auvil, Constanze Hampel, Panos Z Anastasiadis, Bhaskar Kallakury, Aykut Uren, David W Foley, Milton L Brown, Lawrence Shapiro, Michael Brenner, David Haigh, Stephen W Byers
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 6 Pg. 1458-74 (Mar 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 24681547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Cadherins
• Cyclooxygenase 2 Inhibitors
• Pyrazoles
• RNA, Messenger
• RNA, Small Interfering
• Sulfonamides
• osteoblast cadherin
• Celecoxib

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Apoptosis (drug effects)
• Arthritis, Rheumatoid (drug therapy, metabolism, pathology)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cadherins (antagonists & inhibitors, genetics, metabolism)
• Carcinoma, Basal Cell (drug therapy, metabolism, pathology)
• Carcinoma, Ductal, Breast (drug therapy, metabolism, pathology)
• Carcinoma, Intraductal, Noninfiltrating (drug therapy, metabolism, pathology)
• Carcinoma, Lobular (drug therapy, metabolism, pathology)
• Celecoxib
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Female
• Flow Cytometry
• Humans
• Immunoenzyme Techniques
• Mice
• Mice, Nude
• Pyrazoles (pharmacology)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Sulfonamides (pharmacology)
• Surface Plasmon Resonance
• Tumor Cells, Cultured
• Tumor Stem Cell Assay
• Xenograft Model Antitumor Assays