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.
Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, ON, Canada.
Eur J Cancer. 2014 Mar;50(4):713-21. doi: 10.1016/j.ejca.2012.07.019. Epub 2012 Aug 20.
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.
癌胚抗原相关细胞粘附分子 6（CEACAM6）在胰腺癌细胞中过表达，与胰腺癌的进展有关。我们测试了一种针对 CEACAM6 的单域抗体（sdAb）2A3，它是从前一个骆驼科动物免疫文库中分离出来的，以及该 sdAb 的 Fc 缀合物，以确定它们如何影响胰腺癌细胞系 BxPC3。我们还比较了这些抗体与吉西他滨的作用。吉西他滨和 2A3 减缓了癌细胞的增殖。然而，只有 2A3 抑制了癌细胞的侵袭、肿瘤内血管生成和 BxPC3 细胞 MMP-9 活性，这三个特征对肿瘤生长和转移都很重要。2A3、2A3-Fc 和吉西他滨的 IC50 分别为 6.5μM、8μM 和 12nM。虽然与未经处理的对照细胞相比，2A3 抗体抑制了 MMP-9 活性 33%，但吉西他滨未能抑制 MMP-9 活性。此外，2A3 和 2A3-Fc 抑制了 BxPC3 的侵袭，与未经处理的细胞相比，抑制率分别为 73%。当使用用 2A3 或 2A3-Fc 处理的 BxPC3 细胞产生的条件培养基进行毛细管形成测定时，毛细管长度分别减少了 21%和 49%。因此，2A3 是治疗过度表达 CEACAM6 的肿瘤的理想候选药物。
