Your browser doesn't support javascript.
loading
GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development.
Beaumont, Joel E J; Ju, Jinzhe; Barbeau, Lydie M O; Demers, Imke; Savelkouls, Kim G; Derks, Kasper; Bouwman, Freek G; Wauben, Marca H M; Zonneveld, Marijke I; Keulers, Tom G H; Rouschop, Kasper M A.
Afiliación
  • Beaumont JEJ; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Ju J; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Barbeau LMO; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Demers I; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Pathology, GROW-School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Savelkouls KG; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Derks K; Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Bouwman FG; Department of Human Biology, NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Wauben MHM; Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • Zonneveld MI; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Keulers TGH; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
  • Rouschop KMA; Department of Radiotherapy, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands. Electronic address: kasper.rouschop@maastrichtuniversity.nl.
Radiother Oncol ; 190: 109968, 2024 Jan.
Article en En | MEDLINE | ID: mdl-37898438
BACKGROUND AND PURPOSE: Hypoxia is a common feature of tumours, associated with poor prognosis due to increased resistance to radio- and chemotherapy and enhanced metastasis development. Previously we demonstrated that GABARAPL1 is required for the secretion of extracellular vesicles (EV) with pro-angiogenic properties during hypoxia. Here, we explored the role of GABARAPL1+ EV in the metastatic cascade. MATERIALS AND METHODS: GABARAPL1 deficient or control MDA-MB-231 cells were injected in murine mammary fat pads. Lungs were dissected and analysed for human cytokeratin 18. EV from control and GABARAPL1 deficient cells exposed to normoxia (21% O2) or hypoxia (O2 < 0.02%) were isolated and analysed by immunoblot, nanoparticle tracking analysis, high resolution flow cytometry, mass spectrometry and next-generation sequencing. Cellular migration and invasion were analysed using scratch assays and transwell-invasion assays, respectively. RESULTS: The number of pulmonary metastases derived from GABARAPL1 deficient tumours decreased by 84%. GABARAPL1 deficient cells migrate slower but display a comparable invasive capacity. Both normoxic and hypoxic EV contain proteins and miRNAs associated with metastasis development and, in line, increase cancer cell invasiveness. Although GABARAPL1 deficiency alters EV content, it does not alter the EV-induced increase in cancer cell invasiveness. CONCLUSION: GABARAPL1 is essential for metastasis development. This is unrelated to changes in migration and invasion and suggests that GABARAPL1 or GABARAPL1+ EV are essential in other processes related to the metastatic cascade.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares / Neoplasias Límite: Animals / Humans Idioma: En Revista: Radiother Oncol Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Vesículas Extracelulares / Neoplasias Límite: Animals / Humans Idioma: En Revista: Radiother Oncol Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda