Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer

• Published in: Cancer Immunology, Immunotherapy Vol. 64; no. 5; pp. 531 - 537
• Main Authors: Jensen-Jarolim, Erika, Fazekas, Judit, Singer, Josef, Hofstetter, Gerlinde, Oida, Kumiko, Matsuda, Hiroshi, Tanaka, Akane
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2015
• Subjects: Animals; B-Lymphocytes, Regulatory - immunology; Cancer Research; Carcinoembryonic Antigen - metabolism; Dog Diseases - immunology; Dogs; Epithelial-Mesenchymal Transition; Humans; I-kappa B Kinase - metabolism; Immunology; Medicine; Medicine & Public Health; Neoplasms - immunology; Neoplasms - veterinary; NF-kappa B - metabolism; Oncology; Protein Binding; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Review; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - metabolism; Cancer immunology; Regulatory; Nuclear factor kappa-B (NFκB); Transforming growth factor beta (TGF-β); CEA-receptor (CEAR); Carcinoembryonic antigen (CEA)
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-015-1684-6

There is accumulating evidence that the transforming growth factor beta (TGF-β) and nuclear factor kappa-B (NFκB) pathways are tightly connected and play a key role in malignant transformation in cancer. Immune infiltration by regulatory T- and B-lymphocytes (Tregs, Bregs) has recently gained increased attention for being an important source of TGF-β. There is a plethora of studies examining the pro-tumorigenic functions of carcinoembryonic antigen (CEA), but its receptor CEAR is far less studied. So far, there is a single connecting report that TGF-β also may signal through CEAR. The crosstalk between cancer tissues is further complicated by the expression of CEAR and TGF-β receptors in stromal cells, and implications of TGF-β in epithelial–mesenchymal transition. Furthermore, tumor-infiltrating Tregs and Bregs may directly instruct cancer cells by secreting TGF-β binding to their CEAR. Therefore, both TGF-β and CEA may act synergistically in breast cancer and cause disease progression, and NFκB could be a common crossing point between their signaling. CEAR, TGF-β1–3, TGF-β-R types I–III and NFκB class I and II molecules have an outstanding human–canine sequence identity, and only a canine CEA homolog has not yet been identified. For these reasons, the dog may be a valid translational model patient for investigating the crosstalk of the interconnected CEA and TGF-β networks.