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M. Meister
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-034 - The Pregnancy Associated Endometrial Protein Glycodelin as a Biomarker for Malignant Pleural Mesothelioma (ID 5422)
14:30 - 14:30 | Author(s): M. Meister
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. MPM is mainly associated with asbestos exposure and a strong inflammatory reaction. The common treatment of MPM combines macroscopic complete resection and adjuvant or neoadjuvant chemotherapy, respectively. Soluble mesothelin and osteopontin are current available biomarker for malignant mesothelioma with moderate sensitivity and specificity. Glycodelin is an immune system modulator well described during pregnancy. It is involved in invasion of the trophoblast and in regulation of the immunotolerance between the maternal immune system and the fetus.
Methods:
With a commercial ELISA, we measured the glycodelin serum concentrations of patients with MPM. In addition, we analyzed the glycodelin gene expression using quantitative PCR and stained glycodelin in formalin-fixed paraffin embedded tissue slides.
Results:
We found high glycodelin concentrations in the serum of patients with MPM compared to benign lung diseases. Patients with high glycodelin serum concentrations exhibited a worse overall survival. Moreover, glycodelin serum levels correlated with tumor response to treatment. A comparison of soluble mesothelin-related proteins (SMRP) and glycodelin in the serum of a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin mRNA and protein was highly expressed in MPM tumors compared to normal lung tissue.
Conclusion:
In this study, we first described the expression of glycodelin in MPM. Altogether, glycodelin seems to be a new potential serum biomarker for the aggressive malignant pleural mesothelioma.
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P2.01-059 - Regulation of Glycodelin Expression - An Immunomodulatory and Pregnancy Associated Protein in NSCLC (ID 5345)
14:30 - 14:30 | Author(s): M. Meister
- Abstract
Background:
Glycodelin (gene name: progesterone-associated endometrial protein, PAEP) is a protein initially described as an immune system modulator during the establishment of pregnancy. Former studies determined an atypical expression and secretion of glycodelin in non-small cell lung cancer (NSCLC), the most common type of lung cancer. To date, there is not much known about the signaling pathway which regulates PAEP/glycodelin expression in cancer. However, initial experiments already revealed an inducing effect of epidermal growth factor (EGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), lysophosphatidic acid (LPA) and Phorbol 12-myristate 13 acetate (PMA) on PAEP/glycodelin expression in two NSCLC cell lines (H1975 and 2106T). In this study, we analyzed an extended number of possible regulatory candidates to acquire a more detailed view on the regulatory pathway of PAEP/glycodelin in NSCLC.
Methods:
A lung adenocarcinoma (H1975) and a lung squamous cell carcinoma cell line (2106T) were transfected with siRNA targeting nuclear factor κB1 (NFκB1) or treated with human chorionic gonadotropin (hCG), transforming growth factor-β (TGF-β) 1, -2, -3, protein kinase C (PKC) activator bryostatin 1 and PKC inhibitor GF109203x, respectively. Additionally, combined treatments with GF109203x and TGF-β 1,-2, EGF or HB-EGF were performed. PAEP expression in the manipulated cells was determined by quantitative polymerase chain reaction (qPCR), while glycodelin expression or secretion was detected by western blot analysis.
Results:
NFκB1 siRNA transfection resulted in decreased PAEP and glycodelin amounts (H1975 and 2106T), whereas hCG (H1975 and 2106T) and TGF-β 1, -2, -3 (2106T) treatment led to higher levels. In bryostatin treated cells (H1975 and 2106T), PAEP/glycodelin expression was upregulated. The contradictory effect could be demonstrated for cells treated with the PKC inhibitor GF109203x alone and in combination with TGF-β 1,-2, EGF or HB-EGF (H1975 and 2106T).
Conclusion:
This study revealed that there are different regulation mechanisms of PAEP/glycodelin induction in NSCLC. Especially, PKC seems to be involved as a key molecule. The investigated candidates which play a crucial role in driving this signaling pathway are all known to promote the development of cancer. Elucidating the regulatory pathway of the immune system modulating protein glycodelin might reveal a potential strategy to weaken the immune system defense of lung tumors.
