Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells.

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is over-expressed in pancreatic cancer cells, and it is associated with the progression of pancreatic cancer. We tested a single domain antibody (sdAb) targeting CEACAM6, 2A3, which was isolated previously from a llama immune library, and an Fc conjugated version of this sdAb, to determine how they affect the pancreatic cancer cell line BxPC3. We also compared the effects of the antibodies to gemcitabine. Gemcitabine and 2A3 slowed down cancer cell proliferation. However, only 2A3 retarded cancer cell invasion, angiogenesis within the cancer mass and BxPC3 cell MMP-9 activity, three features important for tumour growth and metastasis. The IC50s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5μM, 8μM and 12nM, respectively. While the 2A3 antibody inhibited MMP-9 activity by 33% compared to non-treated control cells, gemcitabine failed to inhibit MMP-9 activity. Moreover, 2A3 and 2A3-Fc inhibited invasion of BxPC3 by 73% compared to non-treated cells. When conditioned media that were produced using 2A3- or 2A3-Fc-treated BxPC3 cells were used in a capillary formation assay, the capillary length was reduced by 21% and 49%, respectively. Therefore 2A3 is an ideal candidate for treating tumours that over-express CEACAM6.

• Authors: Tsai-Mu Cheng, Yanal M Murad, Chia-Ching Chang, Ming-Chi Yang, Toya Nath Baral, Aaron Cowan, Shin-Hua Tseng, Andrew Wong, Roger Mackenzie, Dar-Bin Shieh, Jianbing Zhang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 50 Issue 4 Pg. 713-21 (Mar 2014) ISSN: 1879-0852 [Electronic] England
• PMID: 22918079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, CD
• CEACAM6 protein, human
• Cell Adhesion Molecules
• GPI-Linked Proteins
• Single-Domain Antibodies

Topics

• Animals
• Antigens, CD (immunology)
• Camelids, New World
• Carcinoma, Pancreatic Ductal (blood supply, pathology)
• Cell Adhesion Molecules (immunology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Drug Evaluation, Preclinical
• GPI-Linked Proteins (immunology)
• Human Umbilical Vein Endothelial Cells (drug effects, physiology)
• Humans
• Neoplasm Invasiveness
• Neovascularization, Pathologic (pathology, prevention & control)
• Neovascularization, Physiologic (drug effects)
• Pancreatic Neoplasms (blood supply, pathology)
• Single-Domain Antibodies (pharmacology)