Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation,migration, invasion and angiogenesis of pancreatic cancer cells |
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| Affiliation: | 1. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan, ROC;2. Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada;3. Institute of Physics, Academia Sinica, Taipei 10529, Taiwan, ROC;4. Life Science Group, Scientific Research Division, National Synchrotron Radiation Research Center, Hsinchu, Taiwan, ROC;5. Institute of Oral Medicine, College of Medicine and Hospital, National Cheng Kung University, Taiwan 70101;3. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;4. Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada;5. Vrije Universiteit Brussel, Structural Biology Research Center, VIB, 1050 Brussels, Belgium;6. Nanobody Service Facility, VIB, 1050 Brussels, Belgium;1. The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, PR China;2. Jiangsu Nanobody Engineering and Research Center, Nantong 226010, PR China;3. College of 543Biotechnology and Pharmaceutical Engineering, Nanjing University of 544Technology, Nanjing 210009, PR China;4. Institute of Food Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, PR China;1. Biomolecular Analysis, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands;2. Division of BioAnalytical Chemistry, AIMMS research group BioMolecular Analysis, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands;3. Division of Cell Biology, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands;4. Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands;1. Key Laboratory of Child Development and Learning Science (Ministry of Education), Research Center for Learning Science, Southeast University, Nanjing 210096, P.R. China;2. The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, P.R. China;3. Jiangsu Nanobody Engineering and Research Center, Nantong 226010, P.R. China;1. Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave. SW, Washington, DC 20375, USA;2. NOVA Research Inc., 1900 Elkin St., Suite 230, Alexandria, VA 22308, USA;3. Science and Engineering Apprenticeship Program, American Society for Engineering Education, 4555 Overlook Ave. SW, Washington, DC 20375, USA |
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| 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 6.5 μM, 8 μM and 12 nM, 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. |
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