CEACAM6 Specific Neutra™ Antibody Products

CEACAM6 (Carcinoembryonic antigen-related cell adhesion molecule 6, also named as CD66c and NCA-90), is a 344 aa GPI-anchored cell surface glycoprotein belonging to the carcinoembryonic antigen (CEA) family, which is linked to the membrane via a glycosyl phosphatidyl inositol (GPI) linkage and acts as an intercellular cell adhesion molecule. CEACAM6 is composed of an extracellular N-terminus Ig-like V-type domain responsible for the homophilic and heterophilic intercellular adhesion, a membrane-linked glycoprotein, and two N-terminus IgC-like domains.

Its Gene ID: 4680, UniProtKB ID: P40199, and OMIM ID: 163980.

CEACAM6 Functions and Signaling Pathways

CEACAM6 is distributed in a wide range of epithelial cells and myeloid, and its overexpression is reported at the apical/luminal membranes of many tumors. CEACAM6 acts as a regulator of tumor progression and up-regulates multiple activities of cancer, including invasion, metastasis, abnormal proliferation, anti-apoptosis, angiogenesis, and resistance.

As N-terminus domain determines the binding ability of CEACAM6 to other CEACAMs, like CEACAM1, CEA, and CEACAM8, and the bacterial proteins, or itself. There are many upstream regulators modulating the transcriptional expression of CEACAM6, including miR-26a, miR-146, miR-29a/b/c, miR-1256, miR-128, the CD151/TGF-β1/Smad3 axis, and DNA methylation. For downstream signaling pathways, CEACAM6 enhances the proliferation of tumors by up-regulating the expression levels of cyclin-dependent kinase 4 proteins and cyclin D1. CEACAM6 is also found to be involved in the activation of the SRC/focal adhesion kinase/PI3K/AKT and ERK1/2/MAPK pathways directly or indirectly (through EGFR), thus stimulating subsequent tumor invasion, proliferation, migration, angiogenesis, and resistance to anoikis and chemotherapy.

Fig.1 Downstream molecular interaction network regulated by CEACAM6.^{1, 3}

CEACAM6-Targeting Antibodies

Since CEACAM6 is closely associated with a variety of activities of tumors, previous studies have proven that CEACAM6 inhibition reactivates the antitumor response of T cells. Therefore, CEACAM6 has been regarded as a valid biomarker for research, diagnosis, and therapy for cancer, and targeting CEACAM6 has also attracted increasing attention as a strategy for different immunotherapies.

In models of lung cancer, it is reported that different antibodies against CEACAM6 suppress cell viability, tumor invasion, and tumor migration by inhibiting Src/FAK phosphorylation. In models of pancreatic adenocarcinoma, the use of monoclonal antibodies (mAb) targeting CEACAM6 combined with secondary antibodies enhances the sensitivity of cells to cytotoxicity. Another study on lung adenocarcinoma mice model has shown that a combined treatment of an anti-CEACAM6 mAb and paclitaxel significantly inhibits tumor growth.

In addition, humanized single-chain antibody variable fragments (scFv) targeting CEACAM6, or specific CEACAM6-single domain antibodies (sdAB) have also been reported to be potential strategies for therapeutics development, exhibiting antitumor effects and inhibiting cell growth. Moreover, CEACAM6 is also utilized to develop antibody-drug conjugates (ADC), which has gained encouraging preclinical results in pancreatic cancer.

Fig.2 Combined treatment of anti-CEACAM6 mAb and paclitaxel markedly inhibits tumor growth.^{2, 3}

Creative Biolabs offers different anti-CEACAM6 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of CEACAM6-based neutralizing antibodies is also available for you here.

REFERENCES

1. Ru, Guo-Qing, et al. "CEACAM6 is a prognostic biomarker and potential therapeutic target for gastric carcinoma." Oncotarget 8.48 (2017): 83673.
2. Hong, Kwon Pyo, et al. "Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity." Biomaterials 67 (2015): 32-41.
3. Distributed under open access license CC BY 4.0, without modification.