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CD47 also known as integrin associated protein is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 and signal-regulatory protein alpha.

The mechanism by which endometriosis-associated ovarian cancer (EAOC) avoids anti-tumor immune surveillance by macrophages remains unclear, but CD47 is a very important immune checkpoint for macrophage phagocytosis. Therefore, we collected 36 clinical ovarian samples and detected the protein profile of CD47 by immunohistochemistry and analyzed the correlation with clinical pathological features using statistical software. We found that CD47 expression was relatively higher in patients with EAOC compared with the normal group. High CD47 expression was positively and significantly correlated with histology (P = 0.007) and tumor grade (P = 0.002). We also found that CD47 overexpression promotes cancer cell growth and motility in the TOV-112D and TOV-21G cell lines. Silencing CD47 and anti-CD47 mAb inhibit cancer cell growth and motility in cancer cell lines. Together, these results demonstrate that CD47 in EAOC may be a useful surface marker and offer a novel therapeutic option by targeting CD47 in ovarian cancer 1).

2: Feng M, Jiang W, Kim BYS, Zhang CC, Fu YX, Weissman IL. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat Rev Cancer. 2019 Aug 28. doi: 10.1038/s41568-019-0183-z. [Epub ahead of print] Review. PubMed PMID: 31462760.

3: Chen S, Mei S, Hu X. Letter by Chen et al Regarding Article, “Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage”. Stroke. 2019 Sep;50(9):e265. doi: 10.1161/STROKEAHA.119.026469. Epub 2019 Jul 10. PubMed PMID: 31288668.

4: Hua Y, Keep RF, Xi G. Response by Hua et al to Letter Regarding Article, “Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage”. Stroke. 2019 Sep;50(9):e266. doi: 10.1161/STROKEAHA.119.026620. Epub 2019 Jul 10. PubMed PMID: 31288667; PubMed Central PMCID: PMC6710118.

5: Jing C, Bian L, Wang M, Keep RF, Xi G, Hua Y. Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage. Stroke. 2019 Jun;50(6):1539-1547. doi: 10.1161/STROKEAHA.118.024578. Epub 2019 May 14. PubMed PMID: 31084334; PubMed Central PMCID: PMC6538472.

6: Ma D, Liu S, Lal B, Wei S, Wang S, Zhan D, Zhang H, Lee RS, Gao P, Lopez-Bertoni H, Ying M, Li JJ, Laterra J, Wilson MA, Xia S. Extracellular Matrix Protein Tenascin C Increases Phagocytosis Mediated by CD47 Loss of Function in Glioblastoma. Cancer Res. 2019 May 15;79(10):2697-2708. doi: 10.1158/0008-5472.CAN-18-3125. Epub 2019 Mar 21. PubMed PMID: 30898840.

7: Mohanty S, Yerneni K, Theruvath JL, Graef CM, Nejadnik H, Lenkov O, Pisani L, Rosenberg J, Mitra S, Cordero AS, Cheshier S, Daldrup-Link HE. Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma. Cell Death Dis. 2019 Jan 15;10(2):36. doi: 10.1038/s41419-018-1285-3. PubMed PMID: 30674867; PubMed Central PMCID: PMC6367456.

8: Hutter G, Theruvath J, Graef CM, Zhang M, Schoen MK, Manz EM, Bennett ML, Olson A, Azad TD, Sinha R, Chan C, Assad Kahn S, Gholamin S, Wilson C, Grant G, He J, Weissman IL, Mitra SS, Cheshier SH. Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):997-1006. doi: 10.1073/pnas.1721434116. Epub 2019 Jan 2. PubMed PMID: 30602457; PubMed Central PMCID: PMC6338872.

9: Xie T, Liu B, Dai CG, Lu ZH, Dong J, Huang Q. Glioma stem cells reconstruct similar immunoinflammatory microenvironment in different transplant sites and induce malignant transformation of tumor microenvironment cells. J Cancer Res Clin Oncol. 2019 Feb;145(2):321-328. doi: 10.1007/s00432-018-2786-2. Epub 2018 Nov 10. PubMed PMID: 30415302.

10: Li F, Lv B, Liu Y, Hua T, Han J, Sun C, Xu L, Zhang Z, Feng Z, Cai Y, Zou Y, Ke Y, Jiang X. Blocking the CD47-SIRPα axis by delivery of anti-CD47 antibody induces antitumor effects in glioma and glioma stem cells. Oncoimmunology. 2017 Nov 6;7(2):e1391973. doi: 10.1080/2162402X.2017.1391973. eCollection 2018. PubMed PMID: 29308321; PubMed Central PMCID: PMC5749673.

11: Wu X, Luo X, Zhu Q, Zhang J, Liu Y, Luo H, Cheng Y, Xie Z. The Roles of Thrombospondins in Hemorrhagic Stroke. Biomed Res Int. 2017;2017:8403184. doi: 10.1155/2017/8403184. Epub 2017 Oct 30. Review. PubMed PMID: 29214179; PubMed Central PMCID: PMC5682909.

12: Gholamin S, Mitra SS, Feroze AH, Liu J, Kahn SA, Zhang M, Esparza R, Richard C, Ramaswamy V, Remke M, Volkmer AK, Willingham S, Ponnuswami A, McCarty A, Lovelace P, Storm TA, Schubert S, Hutter G, Narayanan C, Chu P, Raabe EH, Harsh G 4th, Taylor MD, Monje M, Cho YJ, Majeti R, Volkmer JP, Fisher PG, Grant G, Steinberg GK, Vogel H, Edwards M, Weissman IL, Cheshier SH. Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med. 2017 Mar 15;9(381). pii: eaaf2968. doi: 10.1126/scitranslmed.aaf2968. PubMed PMID: 28298418.

13: Zhu H, Leiss L, Yang N, Rygh CB, Mitra SS, Cheshier SH, Weissman IL, Huang B, Miletic H, Bjerkvig R, Enger PØ, Li X, Wang J. Surgical debulking promotes recruitment of macrophages and triggers glioblastoma phagocytosis in combination with CD47 blocking immunotherapy. Oncotarget. 2017 Feb 14;8(7):12145-12157. doi: 10.18632/oncotarget.14553. PubMed PMID: 28076333; PubMed Central PMCID: PMC5355332.

14: Zhao S, Yu Z, Liu Y, Bai Y, Jiang Y, van Leyen K, Yang YG, Lok JM, Whalen MJ, Lo EH, Wang X. CD47 deficiency improves neurological outcomes of traumatic brain injury in mice. Neurosci Lett. 2017 Mar 16;643:125-130. doi: 10.1016/j.neulet.2016.12.006. Epub 2016 Dec 5. PubMed PMID: 27931776.

15: Mohme M, Riethdorf S, Pantel K. Circulating and disseminated tumour cells - mechanisms of immune surveillance and escape. Nat Rev Clin Oncol. 2017 Mar;14(3):155-167. doi: 10.1038/nrclinonc.2016.144. Epub 2016 Sep 20. Review. PubMed PMID: 27644321.

16: Kong X, Wang Y, Dai C, Ma W, Wang R. Is CD147 a New Biomarker Reflecting Histological Malignancy of Gliomas? Mol Neurobiol. 2017 Mar;54(2):1568-1576. doi: 10.1007/s12035-016-9894-2. Epub 2016 May 20. PubMed PMID: 27206428.

17: Qie Y, Yuan H, von Roemeling CA, Chen Y, Liu X, Shih KD, Knight JA, Tun HW, Wharen RE, Jiang W, Kim BY. Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes. Sci Rep. 2016 May 19;6:26269. doi: 10.1038/srep26269. Erratum in: Sci Rep. 2016 Aug 01;6:30663. PubMed PMID: 27197045; PubMed Central PMCID: PMC4872535.

18: Cao S, Zheng M, Hua Y, Chen G, Keep RF, Xi G. Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage. Stroke. 2016 Jun;47(6):1626-31. doi: 10.1161/STROKEAHA.116.013146. Epub 2016 Apr 28. PubMed PMID: 27125525; PubMed Central PMCID: PMC5237112.

19: Sun FJ, Zhang CQ, Chen X, Wei YJ, Li S, Liu SY, Zang ZL, He JJ, Guo W, Yang H. Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex. J Neuroinflammation. 2016 Apr 19;13(1):85. doi: 10.1186/s12974-016-0546-2. PubMed PMID: 27095555; PubMed Central PMCID: PMC4837553.

20: Zhang M, Hutter G, Kahn SA, Azad TD, Gholamin S, Xu CY, Liu J, Achrol AS, Richard C, Sommerkamp P, Schoen MK, McCracken MN, Majeti R, Weissman I, Mitra SS, Cheshier SH. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo. PLoS One. 2016 Apr 19;11(4):e0153550. doi: 10.1371/journal.pone.0153550. eCollection 2016. PubMed PMID: 27092773; PubMed Central PMCID: PMC4836698.

21: Ni W, Mao S, Xi G, Keep RF, Hua Y. Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance. Stroke. 2016 Feb;47(2):505-11. doi: 10.1161/STROKEAHA.115.010920. Epub 2016 Jan 5. PubMed PMID: 26732568; PubMed Central PMCID: PMC4729651.

22: Yang SY, Choi SA, Lee JY, Park AK, Wang KC, Phi JH, Koh EJ, Park WY, Park SH, Hwang DW, Jung HW, Kim SK. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47. Oncotarget. 2015 Dec 22;6(41):43712-30. doi: 10.18632/oncotarget.6227. PubMed PMID: 26506238; PubMed Central PMCID: PMC4791261.

23: Park HW, Moon HE, Kim HS, Paek SL, Kim Y, Chang JW, Yang YS, Kim K, Oh W, Hwang JH, Kim JW, Kim DG, Paek SH. Human umbilical cord blood-derived mesenchymal stem cells improve functional recovery through thrombospondin1, pantraxin3, and vascular endothelial growth factor in the ischemic rat brain. J Neurosci Res. 2015 Dec;93(12):1814-25. doi: 10.1002/jnr.23616. Epub 2015 Sep 2. PubMed PMID: 26332684.

24: Zeiner PS, Preusse C, Blank AE, Zachskorn C, Baumgarten P, Caspary L, Braczynski AK, Weissenberger J, Bratzke H, Reiß S, Pennartz S, Winkelmann R, Senft C, Plate KH, Wischhusen J, Stenzel W, Harter PN, Mittelbronn M. MIF Receptor CD74 is Restricted to Microglia/Macrophages, Associated with a M1-Polarized Immune Milieu and Prolonged Patient Survival in Gliomas. Brain Pathol. 2015 Jul;25(4):491-504. doi: 10.1111/bpa.12194. Epub 2014 Nov 20. PubMed PMID: 25175718.

25: Zhou X, Xie Q, Xi G, Keep RF, Hua Y. Brain CD47 expression in a swine model of intracerebral hemorrhage. Brain Res. 2014 Jul 29;1574:70-6. doi: 10.1016/j.brainres.2014.06.003. Epub 2014 Jun 12. PubMed PMID: 24931767; PubMed Central PMCID: PMC4121112.

26: Xing B, Kong YG, Yao Y, Lian W, Wang RZ, Ren ZY. Study on the expression levels of CXCR4, CXCL12, CD44, and CD147 and their potential correlation with invasive behaviors of pituitary adenomas. Biomed Environ Sci. 2013 Jul;26(7):592-8. doi: 10.3967/0895-3988.2013.07.011. PubMed PMID: 23895705.

27: Peev NA, Tonchev AB, Penkowa M, Kalevski SK, Haritonov DG, Chaldakov GN. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients. Acta Neurochir (Wien). 2008 Oct;150(10):1043-8; discussion 1048. doi: 10.1007/s00701-008-0020-8. Epub 2008 Sep 5. PubMed PMID: 18773139.

Wang CL, Lin MJ, Hsu CY, Lin HY, Tsai HP, Long CY, Tsai EM, Hsieh TH, Wu CH. CD47 promotes cell growth and motility in epithelial ovarian cancer. Biomed Pharmacother. 2019 Sep 3;119:109105. doi: 10.1016/j.biopha.2019.109105. [Epub ahead of print] PubMed PMID: 31493748.
cd47.txt · Last modified: 2019/09/08 11:48 by administrador