The human fetoembryonic defense system hypothesis: Twenty years on

Pang, Poh-Choo; Haslam, Stuart M.; Dell, Anne; Clark, Gary F.

doi:10.1016/j.mam.2016.06.002

Cited by 19 publications

(17 citation statements)

References 246 publications

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“…Glycodelin represents one of the foremost examples on how glycosylation dictates the function of a glycoprotein [1,2,8,10,18]. Although protein glycosylation is often altered in cancer [29][30][31][32] nothing is known about the glycosylation of glycodelin in endometrial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…In premenopausal endometrium the expression of glycodelin is temporally regulated by progesterone, expression increasing shortly after ovulation until the end of the menstrual cycle. Depending on the cell of origin glycodelin is differently glycosylated, resulting in glycodelin isoforms with different biological actions [1,[3][4][5][6][7][8]. We have previously characterized four types of glycodelin, which are derived from different reproductive tissues: decidualized endometriumderived glycodelin-A (GdA, isolated from amniotic fluid), glycodelin-F (isolated from follicular fluid), glycodelin-C (isolated from cumulus cells), and seminal vesicle-derived glycodelin-S (GdS, isolated from seminal plasma) [5,7,9,10].…”

Section: Introductionmentioning

confidence: 99%

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Altered glycosylation of glycodelin in endometrial carcinoma

Hautala

Pang

Antonopoulos

et al. 2020

Laboratory Investigation

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Glycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of highmannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Galβ1-4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Altered glycosylation of glycodelin in endometrial carcinoma

Hautala

Pang

Antonopoulos

et al. 2020

Laboratory Investigation

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“…To answer this paradox, Medawar proposed three hypotheses of how a mother supports her fetus in utero, (1) anatomical separation between mother and fetus by the placenta, (2) immaturity of fetal antigens, impairing their ability to elicit a maternal immune response, and (3) immunological inertness of the maternal immune system during pregnancy [7,10]. The mystery of successful gestation is often referred to as "Medawar's Paradox".…”

Section: Medawar's Paradox and Human Pregnancymentioning

confidence: 99%

“…Brazilian-born British biologist Dr. Peter Medawar began his exploration of immunology somewhat by chance. He initially studied nerve regeneration; however, his focus changed when he was enlisted after the start of World War II to study why skin grafts between different individuals were rapidly rejected [1,2]. He used rabbit models of skin transplantation to develop the concept of the immunologic rejection of skin grafts.…”

Section: Introductionmentioning

confidence: 99%

Medawar's Paradox and Immune Mechanisms of Fetomaternal Tolerance

Rendell¹,

Bath²,

Brennan³

2020

OBM Transplantation

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Brazilian-born British biologist Dr. Peter Medawar played an integral role in developing the concepts of immunologic rejection and tolerance, which led to him receiving the Nobel Prize "for the discovery of acquired immunologic tolerance" and eventually made organ transplantation a reality. However, at the time of his early work in tolerance, a paradox to his theories was brought to his attention; how was pregnancy possible? Pregnancy resembles organ transplantation in that the fetus, possessing paternal antigens, is a semiallogeneic graft that can survive without immunosuppression for 9 months. To answer this question, Medawar proposed three hypotheses of how a mother supports her fetus in utero, now known as "Medawar's Paradox." The mechanisms that govern fetomaternal tolerance are still incompletely understood but may provide critical insight into how to achieve immune tolerance in organ transplantation. Here, we review current understanding of the

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“…Exploitation and upregulation of negative costimulatory signaling pathways such as CLTA-4/B7 and PD-/PD-L1 occurs at the feto-maternal interface of the placenta [ 168 ] as well as between tumour/immune cells. In addition, the expression of MUC16 (cancer antigen 125, CA125 [ 169 ]) in the endometrium is thought to prevent uterine NK cells attacking the trophoblast [ 170 ] and upregulation of MUC16 is typically found in ovarian, pancreatic, and other cancers [ 171 , 172 , 173 , 174 ].…”

Section: Cancer and Immune System Interactionsmentioning

confidence: 99%

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

Macpherson

Barry

Ricciardelli

et al. 2020

JCM

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Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still under development and being tested in numerous clinical trials. A detailed understanding of the interactions between cancer and the immune system is vital for optimisation of immunotherapies either alone or when combined with chemotherapy and other therapies. This article, in two main parts, provides an overview of: (1) components of the normal immune system and current knowledge regarding tumour immunology, biology and their interactions; (2) strategies, and targets, together with challenges and potential innovative approaches for cancer immunotherapy, with attention given to epithelial ovarian cancer.

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The human fetoembryonic defense system hypothesis: Twenty years on

Cited by 19 publications

References 246 publications

Altered glycosylation of glycodelin in endometrial carcinoma

Altered glycosylation of glycodelin in endometrial carcinoma

Medawar's Paradox and Immune Mechanisms of Fetomaternal Tolerance

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

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