Expression of Integrin α6β1 Enhances Tumorigenesis in Glioma Cells
Autor: | Sylvie Mathieu, Dominique Figarella-Branger, Jean-Claude Lissitzky, L'Houcine Ouafik, Salma Taboubi, Estelle Delamarre, Véronique Rigot, José Luis, Caroline Berenguer |
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Přispěvatelé: | Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Rok vydání: | 2009 |
Předmět: |
Male
Pathology medicine.medical_specialty Cell Integrin Apoptosis [SDV.CAN]Life Sciences [q-bio]/Cancer Biology medicine.disease_cause Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Glioma medicine Animals Humans Neoplasm Invasiveness U87 neoplasms ComputingMilieux_MISCELLANEOUS Cell Proliferation 030304 developmental biology Mice Inbred BALB C 0303 health sciences Integrin alpha6beta1 Brain Neoplasms Cell growth Cell adhesion molecule medicine.disease 3. Good health medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Female Glioblastoma Carcinogenesis Regular Articles |
Zdroj: | American Journal of Pathology American Journal of Pathology, American Society for Investigative Pathology, 2009, 175 (2), pp.844-855. ⟨10.2353/ajpath.2009.080920⟩ American Journal of Pathology, 2009, 175 (2), pp.844-855. ⟨10.2353/ajpath.2009.080920⟩ |
ISSN: | 0002-9440 1525-2191 |
Popis: | The integrin alpha6beta1 and its main ligand laminin-111 are overexpressed in glioblastoma, as compared with normal brain tissue, suggesting they may be involved in glioblastoma malignancy. To address this question, we stably expressed the alpha6 integrin subunit in the U87 cell line via retroviral-mediated gene transfer. We show that cell surface expression of the alpha6beta1 integrin led to dramatic changes in tumor U87 cell behavior, both in vitro and in vivo. Nude mice receiving either subcutaneous or intracerebral inoculation of alpha6beta1-expressing cells developed substantially more voluminous tumors than mice injected with control cells. The difference in tumor growth was associated with a marked increase in vascularization in response to alpha6beta1 integrin expression and may also be related to changes in the balance between cell proliferation and survival. Indeed, expression of alpha6beta1 enhanced proliferation and decreased apoptosis of U87 cells both in the tumor and in vitro. Additionally, we demonstrate that alpha6beta1 is implicated in glioblastoma cell migration and invasion and that laminin-111 might mediate dissemination of alpha6beta1-positive cells in vivo. Our results highlight for the first time the considerable role of the integrin alpha6beta1 in glioma progression. |
Databáze: | OpenAIRE |
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