CD90与肿瘤关系的研究进展_West China Medical Journal

Authors：

 赵爽 , 景玉婷 ,  李为民

四川大学华西医院呼吸内科（成都 610041）;

Corresponding author：

赵爽, Email: zs_19881103@163.com; 李为民, Email: weimin003@163.com

Keywords：

CD90; 肿瘤干细胞; 肺癌

DOI：

10.7507/1002-0179.20150677

Video：

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恶性肿瘤作为21世纪威胁人类生存和健康的最主要因素，其发病机制尚不清楚，目前仍缺乏特异的诊断方式及有效的治疗手段。“肿瘤干细胞理论”的提出为人们的研究提供了新思路，而CD90作为“肿瘤干细胞”分选的表面标志物已在肝癌、肺癌、神经母细胞瘤等恶性肿瘤中进行了研究，结果表明其可能参与了细胞坏死、凋亡、转移、黏附等多种与肿瘤进展密切相关的过程。同时，CD90作为一种细胞表面的糖蛋白分子，在成纤维细胞、造血干细胞、神经细胞等许多类型的细胞中均有表达，并对细胞与细胞间，细胞与间质间的反应起着调节作用。然而，CD90在肿瘤中的具体作用及相关机制，目前尚存在着争议。现就CD90在肿瘤中的作用及其机制作一综述。

Citation： 赵爽, 景玉婷, 李为民. CD90与肿瘤关系的研究进展. West China Medical Journal, 2015, 30(12): 2356-2359. doi: 10.7507/1002-0179.20150677 Copy

1.	Siegel R, Naishadham D, Jemal A. Cancer statistics[J]. JAMA, 2013, 310(9):982.
2.	Reif AE, Allen JM. The akr thymic antigen and its distribution in leukemias and nervous tissues[J]. JEM, 1964, 120(3):413-433.
3.	Schlesinger M, Yron I. Antigenic changes in lymph-node cells after administration of antiserum to thymus cells[J]. Science, 1969, 164(3886):1412-1413.
4.	Ades EW, Zwerner RK, Acton RT, et al. Isolation and partial characterization of the human homologue of Thy-1[J]. J Exp Med, 1980, 151(2):400-406.
5.	Schanberg LE, Fleenor DE, Kurtzberg J, et al. Isolation and characterization of the genomic human CD7 gene:structural similarity with the murine Thy-1 gene[J]. Proc Natl Acad Sci USA, 1991, 88(2):603-607.
6.	Lehmann GM, Woeller CF, Pollock SJ, et al. Novel anti-adipogenic activity produced by human fibroblasts[J]. Am J Physiol Cell Physiol, 2010, 299(3):C672-C681.
7.	Takeda H, Yamamoto M, Morita N, et al. Relationship between Thy-1 expression and cell-cycle distribution in human bone marrow hematopoietic progenitors[J]. Am J Hematol, 2005, 79(3):187-193.
8.	Nicola T, Hagood JS, James ML, et al. Loss of Thy-1 inhibits alveolar development in the newborn mouse lung[J]. Am J Physiol Lung Cell Mol Physiol, 2009, 296(5):L738-L750.
9.	Oishi K, Ito-Dufros Y. Angiogenic potential of CD44⁺ CD90⁺ multipotent CNS stem cells in vitro[J]. Biochem Biophys Res Commun, 2006, 349(3):1065-1072.
10.	Wang P, Gao Q, Suo Z, et al. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines[J]. PLoS One, 2013, 8(3):e57020.
11.	Fiegel HC, Bruns H, Höper C, et al. Cell growth and differentiation of different hepatic cells isolated from fetal rat liver in vitro[J]. Tissue Eng, 2006, 12(1):123-130.
12.	Zhu J, Thakolwiboon S, Liu X, et al. Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment[J]. PLoS One, 2014, 9(12):e115507.
13.	Abeysinghe HR, Pollock SJ, Guckert NL, et al. The role of the THY1 gene in human ovarian cancer suppression based on transfection studies[J]. Cancer Genet Cytogenet, 2004, 149(1):1-10.
14.	Lung HL, Cheung AK, Cheng Y, et al. Functional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma[J]. Int J Cancer, 2010, 127:304-312.
15.	Fujita N, Kato Y, Naito M, et al. A novel anti-Thy-1 (CD90) monoclonal antibody induces apoptosis in mouse malignant T-lymphoma cells in spite of inducing bcl-2 expression[J]. Int J Cancer, 1996, 66(4):544-550.
16.	Narisawa-Saito M, Yamanashi Y, Morioka T, et al. Thy-1 molecule associates with protein tyrosine kinase(s) in rat mesangial cells[J]. Clin Exp Immunol, 1996, 106(1):86-90.
17.	Zhu GC, Gao L, He J, et al. CD90 is upregulated in gastric cancer tissues and inhibits gastric cancer cell apoptosis by modulating the expression level of SPARC protein[J]. Oncol Rep, 2015, 34(5):2497-2506.
18.	Cheng BQ, Jiang Y, Zhu Q, et al. Wnt/β-catenin aids in regulating the proliferation of hepG2 cells mediated by thy-1[J]. Genet Mol Res, 2014, 13(3):5115-5127.
19.	Mosley K, Collar J, Cattell V. Mesangial cell necrosis in Thy-1 glomerulonephritis——an ultrastructural study[J]. Virchows Arch, 2000, 436(6):567-573.
20.	Choi J, Leyton L, Nham SU. Characterization of alphaX I-domain binding to Thy-1[J]. Biochem Biophys Res Commun, 2005, 331(2):557-561.
21.	Wetzel A, Chavakis T, Preissner KT, et al. Human Thy-1 (CD90) on activated endothelial cells is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18)[J]. J Immunol, 2004, 172(6):3850-3859.
22.	Leyton L, Schneider P, Labra CV, et al. Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites[J]. Curr Biol, 2001, 11(13):1028-1038.
23.	Saalbach A, Wetzel A, Haustein UF, et al. Interaction of human Thy-1 (CD90) with the integrin alphavbeta3 (CD51/CD61):an important mechanism mediating melanoma cell adhesion to activated endothelium[J]. Oncogene, 2005, 24(29):4710-4720.
24.	Schubert K, Gutknecht D, Köberle M, et al. Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation[J]. Am J Pathol, 2013, 182(1):266-276.
25.	Tang KH, Dai YD, Tong M, et al. A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer[J]. Cancer Res, 2013, 73(7):2322-2332.
26.	Akiyama SK, Olden K, Yamada KM. Fibronectin and integrins in invasion and metastasis[J]. Cancer Metastasis Rev, 1995, 14(3):173-189.
27.	Cohen FE, Novotný J, Sternberg MJ, et al. Analysis of structural similarities between brain Thy-1 antigen and immunoglobulin domains. Evidence for an evolutionary relationship and a hypothesis for its functional significance[J]. Biochem J, 1981, 195(1):31-40.
28.	Barker TH, Hagood JS. Getting a grip on Thy-1 signaling[J]. Biochim Biophys Acta, 2009, 1793(5):921-923.
29.	Oikonomou D, Hassan K, Kaifi JT, et al. Thy-1 as a potential novel diagnostic marker for gastrointestinal stromal tumors[J]. J Cancer Res Clin Oncol, 2007, 133(12):951-955.
30.	Hagood JS, Prabhakaran P, Kumbla P, et al. Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis[J]. Am J Pathol, 2005, 167(2):365-379.
31.	Anders YY, Pardo A, Selman M, et al. Thy-1 promoter hypermethylation:a novel epigenetic pathogenic mechanism in pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2008, 39(5):610-618.
32.	Kawamura K, Hiroshima K, Suzuki T, et al. CD90 is a diagnostic marker to differentiate between malignant pleural mesothelioma and lung carcinoma with immunohistochemistry[J]. Am J Clin Pathol, 2013, 140(4):544-549.
33.	陈晋峰, 张力建, 赵爱莲, 等. 肿瘤标记物在肺癌组织中的异常表达及其对肺癌患者预后的影响[J]. 中华医学杂志, 2005, 85(27):1921-1925.
34.	Matsuwaki R, Ishii G, Zenke Y, et al. Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma[J]. Cancer Sci, 2014, 105(7):905-911.
35.	Pirozzi G, Tirino V, Camerlingo R, et al. Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer[J]. Oncol Rep, 2013, 29(5):1763-1768.
36.	Yan X, Luo H, Zhou X, et al. Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines[J]. Oncol Rep, 2013, 30(6):2733-2740.
37.	Lu JW, Chang JG, Yeh KT, et al. Overexpression of thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis[J]. Acta Histochem, 2011, 113(8):833-838.
38.	Yang ZF, Ho DW, Ng MN, et al. Significance of CD90⁺ cancer stem cells in human liver cancer[J]. Cancer Cell, 2008, 13(2):153-166.
39.	Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer[J]. Hepatology, 2008, 47(3):919-928.
40.	Jia Q, Zhang X, Deng T, et al. Positive correlation of Oct4 and ABCG2 to chemotherapeutic resistance in CD90(+)CD133(+) liver cancer stem cells[J]. Cell Reprogram, 2013, 15(2):143-150.
41.	Sukowati CH, Anfuso B, Torre G, et al. The expression of CD90/Thy-1 in hepatocellular carcinoma:an in vivo and in vitro study[J]. PLoS One, 2013, 8(10):e76830.
42.	Hashimoto N, Tsunedomi R, Yoshimura K, et al. Cancer stem-like sphere cells induced from de-differentiated hepatocellular carcinoma-derived cell lines possess the resistance to anti-cancer drugs[J]. BMC Cancer, 2014, 14:722.
43.	Scognamiglio G, D'antonio A, Rossi G, et al. CD90 expression in atypical meningiomas and meningioma metastasis[J]. Am J Clin Pathol, 2014, 141(6):841-849.
44.	True LD, Zhang H, Ye M, et al. CD90/THY1 is overexpressed in prostate cancer-associated fibroblasts and could serve as a cancer biomarker[J]. Mod Pathol, 2010, 23(10):1346-1356.
45.	Fiegel HC, Kaifi JT, Quaas A, et al. Lack of thy1 (CD90) expression in neuroblastomas is correlated with impaired survival[J]. Pediatr Surg Int, 2008, 24(1):101-105.
46.	杨国奋, 朝葵, 李晓明, 等. 基因在上皮性卵巢癌组织中的表达及其意义[J]. 中华肿瘤杂志, 2009, 31(3):203-207.
47.	Woo SR, Oh YT, An JY, et al. Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness[J]. Anat Cell Biol, 2015, 48(1):44-53.

1. Siegel R, Naishadham D, Jemal A. Cancer statistics[J]. JAMA, 2013, 310(9):982.
2. Reif AE, Allen JM. The akr thymic antigen and its distribution in leukemias and nervous tissues[J]. JEM, 1964, 120(3):413-433.
3. Schlesinger M, Yron I. Antigenic changes in lymph-node cells after administration of antiserum to thymus cells[J]. Science, 1969, 164(3886):1412-1413.
4. Ades EW, Zwerner RK, Acton RT, et al. Isolation and partial characterization of the human homologue of Thy-1[J]. J Exp Med, 1980, 151(2):400-406.
5. Schanberg LE, Fleenor DE, Kurtzberg J, et al. Isolation and characterization of the genomic human CD7 gene:structural similarity with the murine Thy-1 gene[J]. Proc Natl Acad Sci USA, 1991, 88(2):603-607.
6. Lehmann GM, Woeller CF, Pollock SJ, et al. Novel anti-adipogenic activity produced by human fibroblasts[J]. Am J Physiol Cell Physiol, 2010, 299(3):C672-C681.
7. Takeda H, Yamamoto M, Morita N, et al. Relationship between Thy-1 expression and cell-cycle distribution in human bone marrow hematopoietic progenitors[J]. Am J Hematol, 2005, 79(3):187-193.
8. Nicola T, Hagood JS, James ML, et al. Loss of Thy-1 inhibits alveolar development in the newborn mouse lung[J]. Am J Physiol Lung Cell Mol Physiol, 2009, 296(5):L738-L750.
9. Oishi K, Ito-Dufros Y. Angiogenic potential of CD44⁺ CD90⁺ multipotent CNS stem cells in vitro[J]. Biochem Biophys Res Commun, 2006, 349(3):1065-1072.
10. Wang P, Gao Q, Suo Z, et al. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines[J]. PLoS One, 2013, 8(3):e57020.
11. Fiegel HC, Bruns H, Höper C, et al. Cell growth and differentiation of different hepatic cells isolated from fetal rat liver in vitro[J]. Tissue Eng, 2006, 12(1):123-130.
12. Zhu J, Thakolwiboon S, Liu X, et al. Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment[J]. PLoS One, 2014, 9(12):e115507.
13. Abeysinghe HR, Pollock SJ, Guckert NL, et al. The role of the THY1 gene in human ovarian cancer suppression based on transfection studies[J]. Cancer Genet Cytogenet, 2004, 149(1):1-10.
14. Lung HL, Cheung AK, Cheng Y, et al. Functional characterization of THY1 as a tumor suppressor gene with antiinvasive activity in nasopharyngeal carcinoma[J]. Int J Cancer, 2010, 127:304-312.
15. Fujita N, Kato Y, Naito M, et al. A novel anti-Thy-1 (CD90) monoclonal antibody induces apoptosis in mouse malignant T-lymphoma cells in spite of inducing bcl-2 expression[J]. Int J Cancer, 1996, 66(4):544-550.
16. Narisawa-Saito M, Yamanashi Y, Morioka T, et al. Thy-1 molecule associates with protein tyrosine kinase(s) in rat mesangial cells[J]. Clin Exp Immunol, 1996, 106(1):86-90.
17. Zhu GC, Gao L, He J, et al. CD90 is upregulated in gastric cancer tissues and inhibits gastric cancer cell apoptosis by modulating the expression level of SPARC protein[J]. Oncol Rep, 2015, 34(5):2497-2506.
18. Cheng BQ, Jiang Y, Zhu Q, et al. Wnt/β-catenin aids in regulating the proliferation of hepG2 cells mediated by thy-1[J]. Genet Mol Res, 2014, 13(3):5115-5127.
19. Mosley K, Collar J, Cattell V. Mesangial cell necrosis in Thy-1 glomerulonephritis——an ultrastructural study[J]. Virchows Arch, 2000, 436(6):567-573.
20. Choi J, Leyton L, Nham SU. Characterization of alphaX I-domain binding to Thy-1[J]. Biochem Biophys Res Commun, 2005, 331(2):557-561.
21. Wetzel A, Chavakis T, Preissner KT, et al. Human Thy-1 (CD90) on activated endothelial cells is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18)[J]. J Immunol, 2004, 172(6):3850-3859.
22. Leyton L, Schneider P, Labra CV, et al. Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites[J]. Curr Biol, 2001, 11(13):1028-1038.
23. Saalbach A, Wetzel A, Haustein UF, et al. Interaction of human Thy-1 (CD90) with the integrin alphavbeta3 (CD51/CD61):an important mechanism mediating melanoma cell adhesion to activated endothelium[J]. Oncogene, 2005, 24(29):4710-4720.
24. Schubert K, Gutknecht D, Köberle M, et al. Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation[J]. Am J Pathol, 2013, 182(1):266-276.
25. Tang KH, Dai YD, Tong M, et al. A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer[J]. Cancer Res, 2013, 73(7):2322-2332.
26. Akiyama SK, Olden K, Yamada KM. Fibronectin and integrins in invasion and metastasis[J]. Cancer Metastasis Rev, 1995, 14(3):173-189.
27. Cohen FE, Novotný J, Sternberg MJ, et al. Analysis of structural similarities between brain Thy-1 antigen and immunoglobulin domains. Evidence for an evolutionary relationship and a hypothesis for its functional significance[J]. Biochem J, 1981, 195(1):31-40.
28. Barker TH, Hagood JS. Getting a grip on Thy-1 signaling[J]. Biochim Biophys Acta, 2009, 1793(5):921-923.
29. Oikonomou D, Hassan K, Kaifi JT, et al. Thy-1 as a potential novel diagnostic marker for gastrointestinal stromal tumors[J]. J Cancer Res Clin Oncol, 2007, 133(12):951-955.
30. Hagood JS, Prabhakaran P, Kumbla P, et al. Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis[J]. Am J Pathol, 2005, 167(2):365-379.
31. Anders YY, Pardo A, Selman M, et al. Thy-1 promoter hypermethylation:a novel epigenetic pathogenic mechanism in pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2008, 39(5):610-618.
32. Kawamura K, Hiroshima K, Suzuki T, et al. CD90 is a diagnostic marker to differentiate between malignant pleural mesothelioma and lung carcinoma with immunohistochemistry[J]. Am J Clin Pathol, 2013, 140(4):544-549.
33. 陈晋峰, 张力建, 赵爱莲, 等. 肿瘤标记物在肺癌组织中的异常表达及其对肺癌患者预后的影响[J]. 中华医学杂志, 2005, 85(27):1921-1925.
34. Matsuwaki R, Ishii G, Zenke Y, et al. Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N2 lung squamous cell carcinoma[J]. Cancer Sci, 2014, 105(7):905-911.
35. Pirozzi G, Tirino V, Camerlingo R, et al. Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer[J]. Oncol Rep, 2013, 29(5):1763-1768.
36. Yan X, Luo H, Zhou X, et al. Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines[J]. Oncol Rep, 2013, 30(6):2733-2740.
37. Lu JW, Chang JG, Yeh KT, et al. Overexpression of thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis[J]. Acta Histochem, 2011, 113(8):833-838.
38. Yang ZF, Ho DW, Ng MN, et al. Significance of CD90⁺ cancer stem cells in human liver cancer[J]. Cancer Cell, 2008, 13(2):153-166.
39. Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer[J]. Hepatology, 2008, 47(3):919-928.
40. Jia Q, Zhang X, Deng T, et al. Positive correlation of Oct4 and ABCG2 to chemotherapeutic resistance in CD90(+)CD133(+) liver cancer stem cells[J]. Cell Reprogram, 2013, 15(2):143-150.
41. Sukowati CH, Anfuso B, Torre G, et al. The expression of CD90/Thy-1 in hepatocellular carcinoma:an in vivo and in vitro study[J]. PLoS One, 2013, 8(10):e76830.
42. Hashimoto N, Tsunedomi R, Yoshimura K, et al. Cancer stem-like sphere cells induced from de-differentiated hepatocellular carcinoma-derived cell lines possess the resistance to anti-cancer drugs[J]. BMC Cancer, 2014, 14:722.
43. Scognamiglio G, D'antonio A, Rossi G, et al. CD90 expression in atypical meningiomas and meningioma metastasis[J]. Am J Clin Pathol, 2014, 141(6):841-849.
44. True LD, Zhang H, Ye M, et al. CD90/THY1 is overexpressed in prostate cancer-associated fibroblasts and could serve as a cancer biomarker[J]. Mod Pathol, 2010, 23(10):1346-1356.
45. Fiegel HC, Kaifi JT, Quaas A, et al. Lack of thy1 (CD90) expression in neuroblastomas is correlated with impaired survival[J]. Pediatr Surg Int, 2008, 24(1):101-105.
46. 杨国奋, 朝葵, 李晓明, 等. 基因在上皮性卵巢癌组织中的表达及其意义[J]. 中华肿瘤杂志, 2009, 31(3):203-207.
47. Woo SR, Oh YT, An JY, et al. Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness[J]. Anat Cell Biol, 2015, 48(1):44-53.

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