標題: Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells
作者: Cheng, Tsai-Mu
Murad, Yanal M.
Chang, Chia-Ching
Yang, Ming-Chi
Baral, Toya Nath
Cowan, Aaron
Tseng, Shin-Hua
Wong, Andrew
MacKenzie, Roger
Shieh, Dar-Bin
Zhang, Jianbing
生物科技學系
Department of Biological Science and Technology
關鍵字: CEACAM6;Single domain antibodies;Pancreatic cancer;Gemcitabine;Angiogenesis;MMP-9;BxPC3
公開日期: 1-Mar-2014
摘要: 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 metas- tasis. The IC(50)s for 2A3, 2A3-Fc and gemcitabine were determined as 6.5 mu M, 8 mu M 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. (C) 2012 Elsevier Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.ejca.2012.07.019
http://hdl.handle.net/11536/23756
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2012.07.019
期刊: EUROPEAN JOURNAL OF CANCER
Volume: 50
Issue: 4
起始頁: 713
結束頁: 721
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