Research Progress of CD73 in Cancer

  • Shuang Guo Shaanxi University of Chinese Medicine
  • Hongli Liu Shaanxi University of Chinese Medicine
Keywords: CD73, Cancer, Antitumor Therapy, Regulatory Mechanism

Abstract

CD73 (NT5E, extracellular 5' nucleotidase) is a multifunctional glycoprotein encoded by the NT5E gene with a relative molecular weight of 70 kD that can be anchored to the outer surface of cell membranes by glycosyl phosphatidylinositol (GPI).CD73 expression levels are aberrant in breast, colorectal, head and neck squamous cell carcinomas, gastric and hepatocellular carcinomas. However, the possible role and mechanism of CD73 in gastric carcinogenesis and development has not been clarified. In this paper, we will review the multiple roles of CD73 in tumour development, including the clinical significance of CD73, the promotion of tumour growth, metastasis and angiogenesis by CD73, the suppression of immune response by CD73, the regulatory mechanisms of CD73 expression, and the current status of CD73 anti-tumour therapy, with a view to providing a reference for subsequent studies.

References

[1] Burnstock G, Di Virgilio F. Purinergic signalling and cancer. Purinergic Signal. 2013 Dec; 9(4): 491-540.

[2] Bours MJ, Swennen EL, Di Virgilio F, et al. Adenosine 5'-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther. 2006 Nov;112(2):358-404.

[3] Zhang B. Opportunities and challenges for anti-CD73 cancer therapy. Immunotherapy. 2012 Sep;4(9):861-5.

[4] Stagg J. The double-edge sword effect of anti-CD73 cancer therapy. Oncoimmunology. 2012 Mar 1;1(2):217-218.

[5] Inoue Y, Yoshimura K, Kurabe N, et al. Prognostic impact of CD73 and A2A adenosine receptor expression in non-small-cell lung cancer [J]. Oncotarget, 2017, 8(5): 8738-51.

[6] Yu J, Wang X, Lu Q, et al. Extracellular 5'-nucleotidase (CD73) promotes human breast cancer cells growth through AKT/GSK-3beta/beta-catenin/ cyclinD1 signaling pathway [J]. Int J Cancer, 2018, 142(5): 959-67.

[7] Xie M, Qin H, Luo Q, et al. MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73 [J]. BMC Cancer, 2017, 17(1): 305.

[8] Wu R, Chen Y, Li F, et al. Effects of CD73 on human colorectal cancer cell growth in vivo and in vitro [J]. Oncol Rep, 2016, 35(3): 1750-6.

[9] Haun RS, Quick CM, Siegel ER, et al. Bioorthogonal labeling cell-surface proteins expressed in pancreatic cancer cells to identify potential diagnostic/ therapeutic biomarkers [J]. Cancer Biol Ther, 2015, 16(10): 1557-65.

[10] Yang Q, Du J, Zu L. Overexpression of CD73 in prostate cancer is associated with lymph node metastasis [J]. Pathol Oncol Res, 2013, 19(4): 811-4.

[11] Bertoni APS, Bracco PA, De Campos RP, et al. Activity of ecto-5'-nucleotidase (NT5E/CD73) is increased in papillary thyroid carcinoma and its expression is associated with metastatic lymph nodes [J]. Mol Cell Endocrinol, 2019, 479(54-60.

[12] Song Y, Song C, Yang S. Tumor-Suppressive Function of miR-30d-5p in Prostate Cancer Cell Proliferation and Migration by Targeting NT5E [J]. Cancer Biother Radiopharm, 2018, 33(5): 203-11.

[13] Turcotte M, Allard D, Mittal D, et al. CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy [J]. Cancer Res, 2017, 77(20): 5652-63.

[14] Cushman SM, Jiang C, Hatch AJ, et al. Gene expression markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance) [J]. Clin Cancer Res, 2015, 21(5): 1078-86.

[15] Zhao J, Soto LMS, Wang H, Katz MH, Prakas. et al. Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival. Pancreatology. 2021 Aug;21(5):942-949.

[16] Serra S, Horenstein AL, Vaisitti T, et al. CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood. 2011 Dec 1;118(23):6141-52.

[17] Yang Q, Du J, Zu L. Overexpression of CD73 in prostate cancer is associated with lymph node metastasis. Pathol Oncol Res. 2013 Oct;19(4):811-4.

[18] Loi S, Pommey S, Haibe-Kains B, et al. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11091-6.

[19] Wink MR, Tamajusuku AS, Braganhol E, et al. Thyroid hormone upregulates ecto-5'-nucleotidase/CD73 in C6 rat glioma cells. Mol Cell Endocrinol. 2003 Jul 31; 205(1-2):107-14.

[20] Tamajusuku AS, Carrillo-Sepúlveda MA, Braganhol E, et al. Activity and expression of ecto-5'-nucleotidase/CD73 are increased by thyroid Activity and expression of ecto-5'-nucleotidase/CD73 are increased by thyroid hormones in vascular smooth muscle cells. Mol Cell Biochem. 2006 Sep; 289(1-2): 65-72.

[21] Ma XL, Hu B, Tang WG, et al. CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma. j Hematol Oncol. 2020 Feb 5;13(1):11.

[22] Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64.

[23] Allard B, Pommey S, Smyth MJ, et al. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013 Oct 15;19 (20):5626-35.
Published
2023-06-01
Section
Original Research Article