Biological Role, Clinical Significance and Potential Therapeutic Applications of CD157 in Ovarian Cancer
Keywords:Ovarian cancer, CD157, BST-1, tumor marker.
Ovarian cancer is the leading cause of gynecologic cancer-related morbidity and mortality owing to the difficulty in detecting early-stage disease. Despite advances in surgical and chemotherapeutic strategies, only marginal improvement in patient outcome has been achieved. Hence, understanding the biological mechanisms underlying ovarian cancer development and progression is critical for its treatment. We reported that CD157 (also known as BST-1), a NAD-metabolizing ectoenzyme regulating leukocyte diapedesis in inflammatory conditions, is expressed in approximately 90% of epithelial ovarian cancers and high CD157 expression is associated with poor outcome in patients. Our experimental results showed that CD157 controls ovarian cancer progression by promoting mesenchymal differentiation. The increased aggressiveness associated with tumors with high CD157 can be reverted in vitro by CD157 gene silencing, or by monoclonal antibodies that block CD157. The overall picture inferred from our experimental and clinical findings suggests that CD157 could aid diagnosis by classifying ovarian cancers into molecular subtypes with different outcomes, CD157 could also represent a novel candidate as a target of antibody-based therapies. This review summarizes and assesses recent research into the emerging functions of CD157 in the control of ovarian cancer progression..
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60(5): 277-300. http://dx.doi.org/10.3322/caac.20073
Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol 2013; 10(4): 211-24. http://dx.doi.org/10.1038/nrclinonc.2013.5
Yigit R, Massuger LF, Figdor CG, Torensma R. Ovarian cancer creates a suppressive microenvironment to escape immune elimination. Gynecol Oncol 2010; 117(2): 366-72. http://dx.doi.org/10.1016/j.ygyno.2010.01.019
Feki A, Berardi P, Bellingan G, Major A, Krause KH, Petignat P, et al. Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model. Crit Rev OncolHematol 2009; 72(1): 1-9. http://dx.doi.org/10.1016/j.critrevonc.2008.12.003
Malayev Y, Levene R, Gonzalez F. Palliative chemotherapy for malignant ascites secondary to ovarian cancer. Am J Hosp Palliat Care 2012; 29(7): 515-21. http://dx.doi.org/10.1177/1049909111434044
Lo Buono N, Morone S, Parrotta R, Giacomino A, Ortolan E, Funaro A. Ectoenzymes in epithelial ovarian carcinoma: potential diagnostic markers and therapeutic targets. In: Farghaly SA Ed. Ovarian Cancer – Basic science perspective. Rijeka, Croatia: InTech - Open Access Publisher 2011; pp. 245-70.
Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (antiEpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev 2010; 36(6): 458-67. http://dx.doi.org/10.1016/j.ctrv.2010.03.001
Leone RMU, Bellati F, Ruscito I, Gasparri ML, Alessandri F, Venturini PL, et al. Monoclonal antibodies therapies for ovarian cancer. Expert Opin Biol Ther 2013; 13(5): 739-64. http://dx.doi.org/10.1517/14712598.2013.767328
Ferrero E, Malavasi F. Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosylcyclase. J Immunol 1997; 159(8): 3858-65.
Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, et al. Evolution and function of the ADP ribosylcyclase/CD38 gene family in physiology and pathology. Physiol Rev 2008; 88(3): 841-86. http://dx.doi.org/10.1152/physrev.00035.2007
Galione A, Chuang KT. Pyridine nucleotide metabolites and calcium release from intracellular stores. Adv Exp Med Biol 2012; 740: 305-23. http://dx.doi.org/10.1007/978-94-007-2888-2_13
Ishihara K, Hirano T. BST-1/CD157 regulates the humoral immune responses in vivo. Chem Immunol 2000; 75: 235-55. http://dx.doi.org/10.1159/000058772
Lavagno L, Ferrero E, Ortolan E, Malavasi F, Funaro A. CD157 is part of a supramolecular complex with CD11b/CD18 on the human neutrophil cell surface. J Biol Regul Homeost Agents 2007; 21(1-2): 5-11.
Lo Buono N, Parrotta R, Morone S, Bovino P, Nacci G, Ortolan E, et al. The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes. J Biol Chem 2011; 286(21): 18681-91. http://dx.doi.org/10.1074/jbc.M111.227876
Kaisho T, Ishikawa J, Oritani K, Inazawa J, Tomizawa H, Muraoka O, et al. BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth. Proc Natl Acad Sci USA 1994; 91(12): 5325-29. http://dx.doi.org/10.1073/pnas.91.12.5325
Goldstein SC, Todd RF, 3rd. Structural and biosynthetic features of the Mo5 human myeloid differentiation antigen. Tissue Antigens 1993; 41(4): 214-8. http://dx.doi.org/10.1111/j.1399-0039.1993.tb02007.x
Funaro A, Ortolan E, Ferranti B, Gargiulo L, Notaro R, Luzzatto L, et al. CD157 is an important mediator of neutrophil adhesion and migration. Blood 2004; 104(13): 4269-78. http://dx.doi.org/10.1182/blood-2004-06-2129
Ortolan E, Tibaldi EV, Ferranti B, Lavagno L, Garbarino G, Notaro R. et al. CD157 plays a pivotal role in neutrophil transendothelial migration. Blood 2006; 108(13): 4214-22. http://dx.doi.org/10.1182/blood-2006-04-017160
Ortolan E, Vacca P, Capobianco A, Armando E, Crivellin F, Horenstein A, et al. CD157, the Janus of CD38 but with a unique personality. Cell Biochem Funct 2002; 20(4): 309-22. http://dx.doi.org/10.1002/cbf.978
Quarona V, Zaccarello G, Chillemi A, Brunetti E, Singh VK, Ferrero E, et al. CD38 and CD157: A long journey from activation markers to multifunctional molecules. Cytometry B 2013; in press.
Ortolan E, Arisio R, Morone S, Bovino P, Lo-Buono N, Nacci G, et al. Functional Role and Prognostic Significance of CD157 in Ovarian Carcinoma. J Natl Cancer Inst 2010; 105(16): 1160-77. http://dx.doi.org/10.1093/jnci/djq256
Morone S, Lo Buono N, Parrotta R, Giacomino A, Nacci G, Brusco A, et al. Overexpression of CD157 contributes to epithelial ovarian cancer progression by promoting mesenchymal differentiation. PLoS ONE 2012; 7(8): e43649. http://dx.doi.org/10.1371/journal.pone.0043649
Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011; 331(6024): 1559-64. http://dx.doi.org/10.1126/science.1203543
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013; 13(2): 97-110. http://dx.doi.org/10.1038/nrc3447
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-15. http://dx.doi.org/10.1016/j.cell.2008.03.027
Scheel C, Weinberg RA. Cancer stem cells and epithelialmesenchymal transition: concepts and molecular links. Semin Cancer Biol 2012; 22(5-6): 396-403. http://dx.doi.org/10.1016/j.semcancer.2012.04.001
Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res 2009; 69(14): 5627-29. http://dx.doi.org/10.1158/0008-5472.CAN-09-0654
Gao MQ, Choi YP, Kang S, Youn JH, Cho NH. CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 2010; 29(10): 2672-80. http://dx.doi.org/10.1038/onc.2010.35
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008; 8: 755-68. http://dx.doi.org/10.1038/nrc2499
Funaro A, Ortolan E, Bovino P, Lo Buono N, Nacci G, Parrotta R, et al. Ectoenzymes and innate immunity: The role of human CD157 in leukocyte trafficking. Frontiers in Bioscience 2009; 14: 929-43. http://dx.doi.org/10.2741/3287
Ross JA, Ansell I, Hjelle JT, Anderson JD, Miller-Hjelle MA, Dobbie JW. Phenotypic mapping of human mesothelial cells. Adv Perit Dial 1998; 14: 25-30.
Sessa C, Del Conte G. Targeted therapies: tailored treatment for ovarian cancer: are we there yet? Nat Rev Clin Oncol 2010; 7(2): 80-2. http://dx.doi.org/10.1038/nrclinonc.2009.233