The role of biglycan in the tumor microenvironment of malignant melanoma

Hochschulschrift

Abstract: Patients with malignant melanoma have very poor survival rates once the disease reaches metastatic stages. Recent research has highlighted the importance of extracellular matrix organization in tumor development and progression. Biglycan is a proteoglycan, belonging to the family of small leucine-rich proteoglycans. It plays a structural role in several types of connective tissue, binds to collagen and contributes to its remodeling. In the recent years, the role of biglycan as an immunologically active molecule has been increasingly recognized. The role of biglycan in cancer has been assessed in several studies. However, none of them clarified its functional role. Biglycan has never been studied in malignant melanoma. Based on the current knowledge of its role for the immune cell activation and extracellular matrix remodeling, the focus of this thesis was its role in the tumor microenvironment of malignant melanoma. Biglycan was expressed in human melanoma samples, both in the tumor cells, as well as in the tumor stroma. High biglycan staining intensity correlated with poor patient prognosis and shorter overall and progression-free survival. Bgn-/- mice injected with B16 melanoma cells intravenously displayed a significantly delayed tumor growth and survived significantly longer than their wildtype counterparts. Biglycan stimulation increased ERK and JNK phosphorylation in the B16 melanoma cells, as well as transcription of genes responsible for tumor cell motility, integrin signaling and adhesion, neovascularization and metastasis. Its deficiency in the fibroblasts used in organotypic invasion assay caused a significant delay in collagen remodeling and matrix contraction. Decreased matrix stiffness of less contracted Bgn-/- collagen tissue, measured by the atomic force microscopy, resulted in a slower cell migration into this matrix. This correlated with lower integrin β1 expression in the collagen matrices lacking Bgn. Taken together, this study revealed a novel role of the extracellular matrix molecule biglycan for tumor progression of the malignant melanoma, influencing the tumor cells directly, as well as indirectly modulating the tumor microenvironment, especially the characteristics of the extracellular matrix. Moreover, its expression in human melanoma samples and its negative influence on patient prognosis and overall and progression-free survival indicates its possible use as a prognosis-related marker

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: cc_by_nc_nd http://creativecommons.org/licenses/by-nc-nd/4.0/deed.de cc ; Albert-Ludwigs-Universität Freiburg, Dissertation, 2017

Klassifikation und Themen

• Klassifikation: Medizin, Gesundheit

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2017
• Urheber: Andrlová, Hana
• Beteiligte Personen und Organisationen: Zeiser, Robert ; Universitätsklinikum Freiburg ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Albert-Ludwigs-Universität Freiburg

Weitere Informationen

• DOI: 10.6094/UNIFR/12963
• URN: urn:nbn:de:bsz:25-freidok-129631
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:45 MEZ