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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DOIResolve DOI: http://doi.org/10.1016/j.ejca.2012.07.019
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TypeArticle
Journal titleEuropean Journal of Cancer
ISSN0959-8049
SubjectCEACAM6; Single domain antibodies; Pancreatic cancer; Gemcitabine; Angiogenesis; MMP-9; BxPC3
AbstractCarcinoembryonic 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.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
IdentifierS0959804912006028
NPARC number21268726
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Record identifier2f24073c-c7d9-48f4-a3c4-cec1d011a85b
Record created2013-11-08
Record modified2016-05-09
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