HLA-G expression in effusions is a possible marker of tumor susceptibility to chemotherapy in ovarian carcinoma

Davidson, Ben; Elstrand, Mari Bukholt; McMaster, Michael; Berner, Aasmund; Kurman, Robert J.; Risberg, Bjørn; Tropé, Claes G.; Shih, Ie Ming

doi:10.1016/j.ygyno.2004.09.049

Cited by 88 publications

(72 citation statements)

References 17 publications

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“…An increase of seric HLA-G levels was observed in patients with melanoma. Recently, HLA-G was demonstrated to be a potential marker in malignant ascites of ovarian and breast carcinoma [9,10]. Among these various human solid tumors analyzed for HLA-G expression, melanoma represents the one in which the largest number of cell lines and surgically removed lesions have been tested.…”

Section: Introductionmentioning

confidence: 99%

Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2′-deoxycytidine

et al. 2005

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The non-classical HLA class I antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance. In melanoma, HLA-G antigen expression has been found in 30% of surgically removed lesions but in less than 1% of established cell lines. One possible mechanism underlying the differential HLA-G expression in vivo and in vitro is that the HLA-G gene is epigenetically repressed in melanoma cells in vitro. To test this hypothesis, we treated the HLA-G negative melanoma cell line OCM-1A with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AC) and analyzed whether HLA-G expression can be restored. Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon. After treatment, HLA-G mRNA expression was dramatically increased. Western blot and flow cytometry showed that HLA-G protein was induced. Interestingly, HLA-G cell surface expression on the 5-AC treated OCM-1A cells is much less than that on the HLA-G positive JEG-3 cells while a similar amount of total HLA-G was observed. Possible mechanisms for the difference were analyzed in the study such as cell cold-treatment, peptide loading and antigen processing machinery components (APM) as well as β 2 microglobulin (β 2 -m) expression. Data revealed that the APM component calreticulin might be involved in the lower HLA-G surface expression on OCM-1A cells. Taken together, our results indicated that DNA methylation is an important epigenetic mechanism by which HLA-G antigen expression is modulated in melanoma cells in vitro. Furthermore, to the first time, we hypothesized that the deficiency of calreticulin might be involved in the low HLA-G surface expression on the 5-AC treated OCM-1A cells.

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Section: Introductionmentioning

confidence: 99%

Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2′-deoxycytidine

et al. 2005

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“…The presence of a high proportion of HLA-G positive tumor cells in effusions obtained before chemotherapy administration correlated with better response to chemotherapy and overall survival. This finding suggests that HLA-G expression by ovarian carcinoma cells in effusions represents a possible marker of tumor susceptibility to chemotherapy [2].…”

Section: Introductionmentioning

confidence: 86%

“…Malignant transformation of cells may be associated with de novo expression of HLA-G, although the frequency of this phenotypic change varies markedly among different types of tumors [1][2][3][4][5][6]. This topic has been discussed in detail in recently published reviews, to which we refer the interested reader [1,3].…”

Section: Introductionmentioning

confidence: 99%

Soluble HLA-G: Are they clinically relevant?

Pistoia¹,

Morandi²,

Wang³

et al. 2007

Seminars in Cancer Biology

161

182

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HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main function in physiological conditions is to abrogate maternal NK cell activity against foetal tissue and to establish immune tolerance at maternal-foetal interface. HLA-G is expressed not only as a membrane bound molecule on the surface of cells, but also as a soluble moiety in body fluids. The major isoforms of HLA-G present in serum are soluble HLA-G1 and HLA-G5 which are generated by shedding or proteolytic cleavage of the membrane bound isoform and by secretion of a soluble isoform, respectively.Here we review the data about soluble HLA-G (sHLA-G) serum levels in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies. In particular, we focus on sHLA-G expression and function in human neuroblastoma, a pediatric tumor, with special emphasis on a novel potential immuno escape mechanism utilized by NB to instruct monocytes to produce and release sHLA-G. Finally, the potential clinical relevance of sHLA-G serum levels is discussed.

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“…8 However, it is not found in other healthy tissues expressing MHC class Ia antigens. In the neoplasm, HLA-G is expressed in all trophoblastic tumors, 9 and in clinical specimens such as melanoma, 10 renal cell carcinoma, 11 carcinoma of the lung, 12 breast carcinoma, 13 lymphomas, 14 ovarian carcinoma, 15 endometrial adenocarcinoma 16 and various gastrointestinal cancers including pancreatic ductal adenocarcinoma, ampullary cancer, biliary cancer and colorectal cancer. 17 HLA-G has been postulated to mediate immunal tolerance during pregnancy by suppressing alloreactive CD4 þ T-cell proliferation 18,19 and inhibiting NK-celland T-cell-mediated cytolysis.…”

mentioning

confidence: 99%

Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer

Ye¹,

Zhang²,

Li³

et al. 2007

Modern Pathology

142

126

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HLA-G expression in effusions is a possible marker of tumor susceptibility to chemotherapy in ovarian carcinoma

Cited by 88 publications

References 17 publications

Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2′-deoxycytidine

Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2′-deoxycytidine

Soluble HLA-G: Are they clinically relevant?

Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer

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