Endoglin and squamous cell carcinomas
Frontiers in Medicine, vol. 10, pp. 1112573
Abstract
Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely unknown. Therefore, we investigated SCC endoglin expression and function in three types of SCCs; head and neck (HNSCC), esophageal (ESCC) and vulvar (VSCC) cancers. Endoglin expression was evaluated in tumor specimens and 14 patient-derived cell lines. Next to being expressed on angiogenic endothelial cells, endoglin is selectively expressed by individual SCC cells in tumor nests. Patient derived HNSCC, ESCC and VSCC cell lines express varying levels of endoglin with high interpatient variation. To assess the function of endoglin in signaling of TGF-β ligands, endoglin was overexpressed or knocked out or the signaling was blocked using TRC105, an endoglin neutralizing antibody. The endoglin ligand BMP-9 induced strong phosphorylation of SMAD1 independent of expression of the type-I receptor ALK1. Interestingly, we observed that endoglin overexpression leads to strongly increased soluble endoglin levels, which in turn decreases BMP-9 signaling. On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.
Authors 11
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Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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Stefanus G. T. Janson Aachen Department of Gastroenterology-Hepatology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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Marjolijn D. Trietsch Aachen Department of Gynecology, Leiden University Medical Center Department of Pathology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Gynecology, Leiden University Medical Center, Leiden, Netherlands
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
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Manon de Graaf Aachen Department of Gastroenterology-Hepatology, Leiden University Medical Center Department of Medical Oncology
Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
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Eveline S. de Jonge-Muller Aachen Department of Gastroenterology-Hepatology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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Jurjen J. Boonstra Aachen Department of Gastroenterology-Hepatology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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Erasmus MC · Erasmus MC Cancer Institute
Affiliation as printed
Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
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Lukas J.A.C. Hawinkels corresponding Aachen Department of Gastroenterology-Hepatology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands
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