Expression of HLA-G in hemangioma and its clinical significance
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Summary
This study examined the roles of HLA-G in the pathogenesis, development and immune tolerance of hemangioma. From 2000 to 2007, 52 paraffin-embedded specimens (26 from males and 26 from females) of skin capillary hemangioma and 7 samples of adjacent normal skin tissues were collected. Four fresh specimens of hemangioma were also harvested. All samples were HE-stained and proliferative cell nuclear antigen (PCNA) was immunohistochemically detected by using SP method. The samples were classified into proliferative group and degenerative group according to the Mulliken criteria and the expression pattern of PCNA. SP method and quantum dots double staining were applied to detect the expression of HLA-G and PCNA in hemangioma and normal tissue samples. The expression of HLA-G was detected by RT-PCR. The results showed that among the 52 samples of hemangioma, 29 were of proliferative type and 23 degenerative type, and of the four fresh samples of hemangioma, 2 were of proliferative type and 2 degenerative type. SP method results showed that HLA-G was expressed in both proliferative and degenerative hemangioma, but not in normal tissues. The quantum dots double staining exhibited that HLA-G expression was significantly higher in proliferative group than in degenerative (P<0.05) and normal groups (P<0.05), but there was no statistically significant difference between the latter two groups (P>0.05). RT-PCR revealed that HLA-G was transcribed in both the proliferative and degenerative hemangioma tissues, but not in normal tissues. We are led to conclude that the elevated expression of HLA-G in proliferative hemangioma cells may lead to immune tolerance, which allows cells to escape immune surveillance and proliferate. On the other hand, the lower expression of HLA-G in degenerative hemangioma may result in immune cells-induced degeneration of hemangioma.
Keywords
hemangioma HLA-G immunohistochemistry quantum dotsPreview
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References
- 1.Ito T, Ito N, Saathoff M, et al. Immunology of the human nail apparatus: the nail matrix is a site of relative immune privilege. J Investig Dermatol, 2005,125(6):1139–1148PubMedCrossRefGoogle Scholar
- 2.Blaschitz A, Lenfant F, Mallet V, et al. Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur J Immunol, 1997,27(12):3380–3388PubMedCrossRefGoogle Scholar
- 3.Jurisicova A, Casper RF, Maclusky NJ, et al. HLA-G expression during preimplantation human embryo development. Proc Natl Acad Sci USA, 1996,93(1):161–165PubMedCrossRefGoogle Scholar
- 4.Le Discorde M, Moreau P, Sabatier P, et al. Expression of HLA-G in human cornea, an immune-privileged tissue. Hum Immunol, 2003,64(11):1039–1044PubMedCrossRefGoogle Scholar
- 5.Mallet V, Blaschitz A, Crisa L, et al. HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein. Int Immunol, 1999, 11(6):889–898PubMedCrossRefGoogle Scholar
- 6.Yao YQ, Barlow DH, Sargent IL. Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses. J Immunol, 2005,175(12):8379–8385PubMedGoogle Scholar
- 7.Davidson B, Elstrand MB, Mcmaster MT, et al. HLA-G expression in effusions is a possible marker of tumor susceptibility to chemotherapy in ovarian carcinoma. Gynecol Oncol, 2005,96(1):42–47PubMedCrossRefGoogle Scholar
- 8.Ibrahim EC, Guerra N, Lacombe MJ, et al. Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma. Cancer Res, 2001,61(18):6838–6845PubMedGoogle Scholar
- 9.Lefebvre S, Antoine M, Uzan S, et al. Specific activation of the non-classical class I histocompatibility HLA-G antigen and expression of the ILT2 inhibitory receptor in human breast cancer. J Pathol, 2002,196(3):266–274PubMedCrossRefGoogle Scholar
- 10.Paul P, Rouas-Freiss N, Khalil-Daher I, et al. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proc Natl Acad Sci USA, 1998,95(8):4510–4515PubMedCrossRefGoogle Scholar
- 11.Rieger L, Hofmeister V, Probe C, et al. Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E. Mol Hum Reprod, 2002,8(3):255–261PubMedCrossRefGoogle Scholar
- 12.Rouas-Freiss N, Moreau P, Ferrone S, et al. HLA-G pro teins in cancer: do they provide tumor cells with an escape mechanism? Cancer Res, 2005,65(22):10139–10144PubMedCrossRefGoogle Scholar
- 13.Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg, 1982,69(3):412–422PubMedCrossRefGoogle Scholar
- 14.Shan SG, Shan G, Zhang DL. Treatment of hemangioma by transfection of antisense VEGF gene. J Huazhong Univ Sci Technol [Med Sci], 2009,29(3):335–339CrossRefGoogle Scholar
- 15.Paul P, Rouas-Freiss N, Moreau P, et al. HLA-G, -E, -F preworkshop: tools and protocols for analysis of non-classical class I genes transcription and protein expression. Hum Immunol, 2000,61(11):1177–1195PubMedCrossRefGoogle Scholar
- 16.Park GM, Lee S, Park B, et al. Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis. Biochem Biophys Res Commun, 2004,313(3):606–611PubMedCrossRefGoogle Scholar
- 17.Teklemariam T, Zhao LM, Basil M, et al. Full-length HLA-G1 and truncated HLA-G3 differentially increase HLA-E surface localization. Hum Immunol, 2012,73(9): 898–905PubMedCrossRefGoogle Scholar
- 18.Fons P, Chabot S, Cartwright JE, et al. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood, 2006,108(8):2608–2615PubMedCrossRefGoogle Scholar
- 19.Gao GF, Willcox BE, Wyer JR, et al. Classical and nonclassical class I major histocompatibility complex molecules exhibit subtle conformational differences that affect binding to CD8alphaalpha. J Biol Chem, 2000,275(20): 15232–15238PubMedCrossRefGoogle Scholar
- 20.López-Botet M, Navarro F, Llano M. How do NK cells sense the expression of HLA-G class Ib molecules? Semin Cancer Biol, 1999,9(1):19–26PubMedCrossRefGoogle Scholar
- 21.Yan WH, Fan LA. Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition. Cell Res, 2005,15(3):176–182PubMedCrossRefGoogle Scholar
- 22.Amiot L, Ferrone S, Grosse-Wilde H, et al. Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention? CMLS, 2011,68(3):417–431PubMedCrossRefGoogle Scholar
- 23.Frumento G, Franchello S, Palmisano GL, et al. Melanomas and melanoma cell lines do not express HLA-G, and the expression cannot be induced by gammaIFN treatment. J Comp Pathol, 2000,56(1):30–37Google Scholar
- 24.Ibrahim EC, Aractingi S, Allory Y, et al. Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype. Int J Cancer, 2004,108(2):243–250PubMedCrossRefGoogle Scholar
- 25.Wlasiuk P, Stec A, Piechnik A, et al. Expression of soluble HLA-G in multiple myeloma patients and patients with renal failure. Leuk Res, 2012,36(7): 881–883PubMedCrossRefGoogle Scholar
- 26.Brahim EC, Aractingi S, Allory Y, et al. Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype. Int J Cancer, 2004,108(2):243–250CrossRefGoogle Scholar
- 27.Wiendl H, Mitsdoerffer M, Hofmeister V, et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J Immunol, 2002,168(9):4772–4780PubMedGoogle Scholar
- 28.Bukur J, Malenica B, Huber C, et al. Altered expression of nonclassical HLA class Ib antigens in human renal cell carcinoma and its association with impaired immune response. Hum Immunol, 2003, 64(11):1081–1092PubMedCrossRefGoogle Scholar
- 29.Maejima M, Fujii T, Kozuma S, et al. Presence of HLA-G-expressing cells modulates the ability of peripheral blood mononuclear cells to release cytokines. Am J Reprod Immunol, 1997,38(2):79–82PubMedCrossRefGoogle Scholar
- 30.Braud VM, Allan DS, O’Callaghan CA, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature, 1998,391(6669):795–799PubMedCrossRefGoogle Scholar
- 31.Urosevic M, Kurrer MO, Kamarashev J, et al. Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class-loss and interleukin-10 production. Am J Pathol, 2001,159(3):817–824PubMedCrossRefGoogle Scholar