CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Aug 7

PMID 34360654

Citations 13

Authors

Minami Sakamoto

Tomomitsu Miyagaki

Hiroaki Kamijo

Tomonori Oka

Hikari Boki

Naomi Takahashi-Shishido

Hiraku Suga

Makoto Sugaya

Shinichi Sato

Affiliations

Soon will be listed here.

Abstract

CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and cyclophilin A (CypA), one of the binding partners of CD147, are overexpressed in tumor cells and associated with the progression of several malignancies, including both solid and hematological malignancies. However, CD147 and CypA involvement in cutaneous T-cell lymphoma (CTCL) has not been reported. In this study, we examined CD147 and CypA expression and function using clinical samples of mycosis fungoides (MF) and Sézary syndrome (SS) and CTCL cell lines. CD147 and CypA were overexpressed by tumor cells of MF/SS, and CypA was also expressed by epidermal keratinocytes in MF/SS lesional skin. Serum CypA levels were increased and correlated with disease severity markers in MF/SS patients. Anti-CD147 antibody and/or anti-CypA antibody suppressed the proliferation of CTCL cell lines, both in vitro and in vivo, via downregulation of phosphorylated extracellular-regulated kinase 1/2 and Akt. These results suggest that CD147-CypA interactions can contribute to the proliferation of MF/SS tumor cells in both a autocrine and paracrine manner, and that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of MF/SS.

Citing Articles

Differential Expression of Neurodegeneration-Related Genes in SH-SY5Y Neuroblastoma Cells Under the Influence of Cyclophilin A: Could the Enzyme be a Likely Trigger and Therapeutic Target for Alzheimer's Disease?.

Pashaei S, Shabani S, Mohammadi S, Morozova-Roche L, Salari N, Rahimi Z Neurochem Res. 2024; 50(1):47.

PMID: 39636462 DOI: 10.1007/s11064-024-04253-2.

Metabolic Function and Therapeutic Potential of CD147 for Hematological Malignancies: An Overview.

Spinello I, Labbaye C, Saulle E Int J Mol Sci. 2024; 25(17).

PMID: 39273126 PMC: 11395103. DOI: 10.3390/ijms25179178.

Engineered CD147-Deficient THP-1 Impairs Monocytic Myeloid-Derived Suppressor Cell Differentiation but Maintains Antibody-Dependent Cellular Phagocytosis Function for Jurkat T-ALL Cells with Humanized Anti-CD147 Antibody.

Pamonsupornwichit T, Sornsuwan K, Juntit O, Yasamut U, Takheaw N, Kasinrerk W Int J Mol Sci. 2024; 25(12).

PMID: 38928332 PMC: 11203531. DOI: 10.3390/ijms25126626.

EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells.

Feigelman G, Simanovich E, Brockmeyer P, Rahat M Front Immunol. 2024; 15:1374088.

PMID: 38725999 PMC: 11079191. DOI: 10.3389/fimmu.2024.1374088.

Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.

Lee H, Hwang S, Jeong E, Chang M J Microbiol. 2024; 62(7):555-568.

PMID: 38700775 PMC: 11303488. DOI: 10.1007/s12275-024-00133-0.

References

Suzuki H, Boki H, Kamijo H, Nakajima R, Oka T, Shishido-Takahashi N . YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways. J Invest Dermatol. 2019; 140(4):860-868.e3. DOI: 10.1016/j.jid.2019.09.007. View

Nabeshima K, Suzumiya J, Nagano M, Ohshima K, Toole B, Tamura K . Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas. J Pathol. 2004; 202(3):341-51. DOI: 10.1002/path.1518. View

Kamijo H, Miyagaki T . Mycosis Fungoides and Sézary Syndrome: Updates and Review of Current Therapy. Curr Treat Options Oncol. 2021; 22(2):10. DOI: 10.1007/s11864-020-00809-w. View

Oka T, Miyagaki T . Novel and Future Therapeutic Drugs for Advanced Mycosis Fungoides and Sézary Syndrome. Front Med (Lausanne). 2019; 6:116. PMC: 6548851. DOI: 10.3389/fmed.2019.00116. View

Thorns C, Feller A, Merz H . EMMPRIN (CD 147) is expressed in Hodgkin's lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases. Anticancer Res. 2002; 22(4):1983-6. View

Arendt B, Walters D, Wu X, Tschumper R, Huddleston P, Henderson K . Increased expression of extracellular matrix metalloproteinase inducer (CD147) in multiple myeloma: role in regulation of myeloma cell proliferation. Leukemia. 2012; 26(10):2286-96. PMC: 3915875. DOI: 10.1038/leu.2012.91. View

Al-Daraji W, Grant K, Ryan K, Saxton A, Reynolds N . Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J Invest Dermatol. 2002; 118(5):779-88. DOI: 10.1046/j.1523-1747.2002.01709.x. View

Han J, Sohng J, Lee W, Oh T, Jung H . Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells. Int J Mol Sci. 2021; 22(5). PMC: 7957809. DOI: 10.3390/ijms22052473. View

Zhu D, Wang Z, Zhao J, Calimeri T, Meng J, Hideshima T . The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat Med. 2015; 21(6):572-80. PMC: 4567046. DOI: 10.1038/nm.3867. View

10.

Mao X, Orchard G, Mitchell T, Oyama N, Russell-Jones R, Vermeer M . A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS. J Cutan Pathol. 2008; 35(10):899-910. DOI: 10.1111/j.1600-0560.2007.00924.x. View

11.

Xu S, Hu C, Xiao Z, Luo C, Liu Z . Downregulation of CyclophilinA/CD147 Axis Induces Cell Apoptosis and Inhibits Glioma Aggressiveness. Biomed Res Int. 2020; 2020:7035847. PMC: 7396009. DOI: 10.1155/2020/7035847. View

12.

Kamijo H, Miyagaki T, Takahashi-Shishido N, Nakajima R, Oka T, Suga H . Thrombospondin-1 promotes tumor progression in cutaneous T-cell lymphoma via CD47. Leukemia. 2019; 34(3):845-856. DOI: 10.1038/s41375-019-0622-6. View

13.

Boki H, Miyagaki T, Shono Y, Kamijo H, Oka T, Suga H . Increased Expression of Delta-like Ligand 4 in Mycosis Fungoides. Acta Derm Venereol. 2020; 100(4):adv00059. PMC: 9128970. DOI: 10.2340/00015555-3402. View

14.

Obchoei S, Sawanyawisuth K, Wongkham C, Kasinrerk W, Yao Q, Chen C . Secreted cyclophilin A mediates G1/S phase transition of cholangiocarcinoma cells via CD147/ERK1/2 pathway. Tumour Biol. 2014; 36(2):849-59. DOI: 10.1007/s13277-014-2691-5. View

15.

Ohtsuka M, Hamada T, Miyagaki T, Shimauchi T, Yonekura K, Kiyohara E . Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020. J Dermatol. 2020; 48(2):e49-e71. DOI: 10.1111/1346-8138.15707. View

16.

Zhang Z, Bian H, Feng Q, Mi L, Mo T, Kuang A . Biodistribution and localization of iodine-131-labeled metuximab in patients with hepatocellular carcinoma. Cancer Biol Ther. 2006; 5(3):318-22. DOI: 10.4161/cbt.5.3.2431. View

17.

Park J, Yang J, Wenzel A, Ramachandran A, Lee W, Daniels J . Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E). Blood. 2017; 130(12):1430-1440. PMC: 5609333. DOI: 10.1182/blood-2017-02-768234. View

18.

Scarisbrick J, Prince H, Vermeer M, Quaglino P, Horwitz S, Porcu P . Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol. 2015; 33(32):3766-73. PMC: 4979132. DOI: 10.1200/JCO.2015.61.7142. View

19.

Obchoei S, Wongkhan S, Wongkham C, Li M, Yao Q, Chen C . Cyclophilin A: potential functions and therapeutic target for human cancer. Med Sci Monit. 2009; 15(11):RA221-32. View

20.

Panchabhai S, Schlam I, Sebastian S, Fonseca R . PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma. Leukemia. 2016; 31(4):991-994. DOI: 10.1038/leu.2016.389. View