The Expression of Serglycin Is Required for Active Transforming Growth Factor ß Receptor I Tumorigenic Signaling in Glioblastoma Cells and Paracrine Activation of Stromal Fibroblasts via CXCR-2.

Manou, Dimitra; Golfinopoulou, Maria-Angeliki; Alharbi, Sara Naif D; Alghamdi, Hind A; Alzahrani, Fatimah Mohammed; Theocharis, Achilleas D

Manou, Dimitra; Golfinopoulou, Maria-Angeliki; Alharbi, Sara Naif D; Alghamdi, Hind A; Alzahrani, Fatimah Mohammed; Theocharis, Achilleas D.

Afiliación

Manou D; Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.
Golfinopoulou MA; Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.
Alharbi SND; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Alghamdi HA; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Alzahrani FM; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Theocharis AD; Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.

Biomolecules ; 14(4)2024 Apr 10.

Article en En | MEDLINE | ID: mdl-38672477

ABSTRACT

ABSTRACT

Serglycin (SRGN) is a pro-tumorigenic proteoglycan expressed and secreted by various aggressive tumors including glioblastoma (GBM). In our study, we investigated the interplay and biological outcomes of SRGN with TGFßRI, CXCR-2 and inflammatory mediators in GBM cells and fibroblasts. SRGN overexpression is associated with poor survival in GBM patients. High SRGN levels also exhibit a positive correlation with increased levels of various inflammatory mediators including members of TGFß signaling pathway, cytokines and receptors including CXCR-2 and proteolytic enzymes in GBM patients. SRGN-suppressed GBM cells show decreased expressions of TGFßRI associated with lower responsiveness to the manipulation of TGFß/TGFßRI pathway and the regulation of pro-tumorigenic properties. Active TGFßRI signaling in control GBM cells promotes their proliferation, invasion, proteolytic and inflammatory potential. Fibroblasts cultured with culture media derived by control SRGN-expressing GBM cells exhibit increased proliferation, migration and overexpression of cytokines and proteolytic enzymes including CXCL-1, IL-8, IL-6, IL-1ß, CCL-20, CCL-2, and MMP-9. Culture media derived by SRGN-suppressed GBM cells fail to induce the above properties to fibroblasts. Importantly, the activation of fibroblasts by GBM cells not only relies on the expression of SRGN in GBM cells but also on active CXCR-2 signaling both in GBM cells and fibroblasts.

Asunto(s)

Fibroblastos; Glioblastoma; Proteoglicanos; Receptores de Interleucina-8B; Transducción de Señal; Proteínas de Transporte Vesicular; Humanos; Glioblastoma/metabolismo; Glioblastoma/patología; Glioblastoma/genética; Receptores de Interleucina-8B/metabolismo; Receptores de Interleucina-8B/genética; Proteoglicanos/metabolismo; Proteoglicanos/genética; Fibroblastos/metabolismo; Fibroblastos/patología; Proteínas de Transporte Vesicular/metabolismo; Proteínas de Transporte Vesicular/genética; Línea Celular Tumoral; Proliferación Celular/genética; Comunicación Paracrina; Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo; Receptor Tipo I de Factor de Crecimiento Transformador beta/genética; Neoplasias Encefálicas/metabolismo; Neoplasias Encefálicas/patología; Neoplasias Encefálicas/genética; Regulación Neoplásica de la Expresión Génica; Células del Estroma/metabolismo; Células del Estroma/patología; Carcinogénesis/genética; Carcinogénesis/metabolismo; Carcinogénesis/patología

Palabras clave

extracellular matrix; glioblastoma; proteoglycans; serglycin; tumor microenvironment

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteoglicanos / Transducción de Señal / Glioblastoma / Receptores de Interleucina-8B / Proteínas de Transporte Vesicular / Fibroblastos Límite: Humans Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Suiza

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