Glycodelin in reproductive endocrinology and hormone-related cancer

Seppälä, Markku; Koistinen, Hannu; Koistinen, Riitta; Hautala, Laura; Chiu, Philip C.N.; Yeung, William S.B.

doi:10.1530/eje-08-0756

Cited by 57 publications

(48 citation statements)

References 111 publications

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“…To date, the expression of glycodelin has been well described mainly in hormone-related tumors such as breast and ovarian cancer (15). Zadran and colleagues (27) recently reported that glycodelin mRNA (PAEP) was one of the most differentially regulated genes in a small cohort of lung ADC patients compared with healthy patients.…”

Section: Discussionmentioning

confidence: 99%

“…Glycodelin A, the immunosuppressive form of glycodelin, functions as a proliferation-suppressor and apoptosis inducer of T cells, monocytes, B cells and NK cells (14). Atypical glycodelin expression is observed in hormone-related breast cancer, endometrial cancer, and ovarian cancer (15). Recent studies have demonstrated glycodelin expression in melanoma cells and lung cancer (16,17).…”

Section: )mentioning

confidence: 99%

“…The role of glycodelin as a regulator of the immune system is well characterized during pregnancy (25) and hormone-related cancer (15). Many studies of glycodelin A have reported immunosuppressive functions.…”

Section: Glycodelin As Well As Immunosuppressive Glycodelin a Is Exprmentioning

confidence: 99%

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Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Schneider

Granzow

Warth

et al. 2015

Clinical Cancer Research

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Purpose: In recent years, immune therapeutic strategies against non–small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer. Experimental Design: In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments, and correlations with clinicopathologic parameters. Results: Glycodelin mRNA expression was significantly elevated in tumors (n = 336) compared with matched normal tissue (P < 0.0001). Overall survival (OS) was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, and the levels correlated with recurrence and metastatic disease. Knockdown of glycodelin with siRNAs in NSCLC cell lines resulted in significant upregulation of immune system modulatory factors such as PDL1, CXCL5, CXCL16, MICA/B, and CD83 as well as proliferation stimulators EDN1 and HBEGF. Furthermore, decreased migration of tumor cells was observed. Conclusions: Altogether, the comprehensive characterization of glycodelin in NSCLC provides strong support for its use as a biomarker with immune modulatory function. Clin Cancer Res; 21(15); 3529–40. ©2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Schneider

Granzow

Warth

et al. 2015

Clinical Cancer Research

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“…It has been demonstrated to be important in a number of physiological processes, such as embryonic implantation, immunotolerance, contraception and gland differentiation. In recent years, several studies have demonstrated that PAEP is abnormally expressed in various types of tumors, such as endometrial carcinoma, ovarian cancer, breast cancer (2)(3)(4)(5), lung cancer (6) and melanoma (7). Transfection of PAEP cDNA into the MCF-7 breast cancer cell line results in marked changes in cell growth behavior, with the suppression of proliferation and formation of acinar structures (8), suggesting that PAEP inhibits tumor cell growth and promotes cell differentiation as a tumor suppressive factor.…”

Section: Introductionmentioning

confidence: 99%

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Chai¹,

Qiao²,

Wang³

et al. 2013

Molecular Medicine Reports

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Abstract. Progestagen-associated endometrial protein (PAEP), also termed glycodelin, is a 28-kDa glycoprotein of the lipocalin superfamily that is expressed in a variety of tumors, including gynecological tumors, lung cancer and melanoma. To determine the biological functions of the PAEP gene in tumor development and progression, the production of transient and stable PAEP knockdown cell models is required. In the present study, RNA interference technology was used to silence PAEP gene expression in melanoma and transfection was screened for and the conditions were optimized using fluorescence microscopy, flow cytometry, qPCR and western blot analysis. The results of the present study showed that the transient transfection of melanoma cells with 100 nmol/l PAEP siRNA or lentiviral PAEP small hairpin RNA (shRNA) [multiplicity of infection (MOI), 100 pfu/cell] efficiently knocked down target gene expression. To establish stable PAEP knockdown cell lines, melanoma cells were infected with a low MOI (10 pfu/cell) of lentiviral particles expressing PAEP shRNA. Following puromycin screening, the PAEP gene knockdown efficiency was demonstrated to be >80% in 624-Mel and 624.38-Mel cell lines, which was validated by western blot analysis. Therefore, melanoma cell lines with stable knockdown of PAEP were successfully established and may be used as effective cell models to study the biological functions of the PAEP gene in melanoma.

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“…Different glycoforms of glycodelin play important roles in regulation of sperm function [3]. Furthermore, glycodelin has immunosuppressive properties, which are thought to protect foetal semiallograft from maternal immune response [4,5].…”

Section: Introductionmentioning

confidence: 99%

Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients

Hautala

Greco

Koistinen

et al. 2010

Breast Cancer Res Treat

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Glycodelin (encoded by PAEP gene) is a secreted lipocalin protein mainly expressed in reproductive tissues, but also in several tumour types. In the breast, glycodelin is expressed both in normal epithelial and cancerous tissue. To investigate the association of glycodelin with clinicopathological features of breast cancer and outcome of patients we evaluated the protein expression of glycodelin in a large series of breast tumours. Immunohistochemical analysis of tissue microarrays was used to study glycodelin expression on 399 sporadic and 436 familial non-BRCA1/2 tumours with strong family history. Gene expression analysis was used to define genes co-expressed with PAEP in sporadic and familial non-BRCA1/2 breast tumours. In the sporadic series, the glycodelin expression associated with low proliferation rate (P < 0.001), with a tendency towards well-differentiated tumours (grades 1 and 2, P = 0.012) and high cyclin D1 (P = 0.034) expression. However, in familial non-BRCA1/2 cases with strong family history glycodelin expression associated with a less favourable phenotype, i.e. positive lymph node status (P = 0.003) and HER2-positive tumours (P = 0.009). Moreover, the patients with glycodelin-positive tumours had an increased risk for distant metastases (P = 0.001) and in multivariate analysis glycodelin expression was an independent predictor of metastasis (hazard ratio (HR) = 2.22, 95% confidence interval (95% CI) = 1.22-4.03, P = 0.009) in familial non-BRCA1/2 breast cancer. Gene expression analysis further revealed different gene expression profiles correlating with the PAEP expression in the sporadic and familial non-BRCA1/2 breast cancers. Our findings suggest differential progression pathways in the sporadic and familial non-BRCA1/2 breast tumours expressing glycodelin.

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Glycodelin in reproductive endocrinology and hormone-related cancer

Cited by 57 publications

References 111 publications

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients

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