Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells.
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.
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan, ROC; Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Tsai-Mu
TM
Cheng
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Yanal M
YM
Murad
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan, ROC; Institute of Physics, Academia Sinica, Taipei 10529, Taiwan, ROC. Electronic address: ccchang01@faculty.nctu.edu.tw.
Chia-Ching
CC
Chang
Life Science Group, Scientific Research Division, National Synchrotron Radiation Research Center, Hsinchu, Taiwan, ROC.
Ming-Chi
MC
Yang
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Toya Nath
TN
Baral
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Aaron
A
Cowan
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan, ROC.
Shin-Hua
SH
Tseng
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Andrew
A
Wong
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Roger
R
Mackenzie
Institute of Oral Medicine, College of Medicine and Hospital, National Cheng Kung University, Taiwan 70101.
Dar-Bin
DB
Shieh
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada. Electronic address: Jianbing.Zhang@nrc-cnrc.gc.ca.
Jianbing
J
Zhang
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002161:Camelids, New World; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D058851:GPI-Linked Proteins / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000473:pathology*; D061905:Single-Domain Antibodies / Q000494:pharmacology*
D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D061905:Single-Domain Antibodies