TY - JOUR
T1 - Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors
T2 - Comparing human and canine cancer
AU - Jensen-Jarolim, Erika
AU - Fazekas, Judit
AU - Singer, Josef
AU - Hofstetter, Gerlinde
AU - Oida, Kumiko
AU - Matsuda, Hiroshi
AU - Tanaka, Akane
N1 - Publisher Copyright:
© The Author(s) 2015.
PY - 2015/5
Y1 - 2015/5
N2 - 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.
AB - 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.
KW - Cancer immunology
KW - Carcinoembryonic antigen (CEA)
KW - CEA-receptor (CEAR)
KW - Nuclear factor kappa-B (NFκB)
KW - Regulatory
KW - Transforming growth factor beta (TGF-β)
KW - Transforming Growth Factor beta/metabolism
KW - Humans
KW - B-Lymphocytes, Regulatory/immunology
KW - T-Lymphocytes, Regulatory/immunology
KW - Carcinoembryonic Antigen/metabolism
KW - I-kappa B Kinase/metabolism
KW - Receptors, Transforming Growth Factor beta/metabolism
KW - Animals
KW - Receptors, Cell Surface/genetics
KW - Dog Diseases/immunology
KW - Dogs
KW - Epithelial-Mesenchymal Transition
KW - Protein Binding
KW - Neoplasms/immunology
KW - NF-kappa B/metabolism
UR - http://www.scopus.com/inward/record.url?scp=84938421142&partnerID=8YFLogxK
U2 - 10.1007/s00262-015-1684-6
DO - 10.1007/s00262-015-1684-6
M3 - Review article
C2 - 25832000
AN - SCOPUS:84938421142
SN - 0340-7004
VL - 64
SP - 531
EP - 537
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 5
ER -