2. Academic Validation
  3. Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spread

Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spread

  • Mol Oncol. 2023 Nov 27. doi: 10.1002/1878-0261.13556.
Núria Gendrau-Sanclemente 1 2,  Agnès Figueras 1 2,  Kristina Gracova 1 2,  Álvaro Lahiguera 1 2,  Elisenda Alsina-Sanchís 1 2,  Juan A Marín-Jiménez 3 4,  August Vidal 2 5 6,  Xavier Matias-Guiu 2 5 6,  Sergi Fernandez-Gonzalez 7,  Marc Barahona 7,  Lola Martí 7,  Jordi Ponce 7,  Francesc Viñals 1 2 8
Affiliations

Affiliations

  • 1 Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO) , Hospital Duran i Reynals, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
  • 2 Oncobell Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
  • 3 Cancer Immunotherapy (CIT) Group-ProCURE, Bellvitge Biomedical Research Institute (IDIBELL) - OncoBell, L'Hospitalet de Llobregat, Barcelona, Spain.
  • 4 Department of Medical Oncology, Catalan Institute of Oncology (ICO) , L'Hospitalet de Llobregat, Barcelona, Spain.
  • 5 Department of Pathology, University Hospital of Bellvitge (IDIBELL) , L'Hospitalet de Llobregat, Barcelona, Spain.
  • 6 CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
  • 7 Department of Gynaecology, University Hospital of Bellvitge (IDIBELL) , L'Hospitalet de Llobregat, Barcelona, Spain.
  • 8 Departament de Ciències Fisiològiques, Universitat de Barcelona, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
PMID: 38010623 DOI: 10.1002/1878-0261.13556
Abstract

High-grade serous ovarian Cancer (HGSOC) is the deadliest gynaecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian Cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRβ) is essential for fibronectin-mediated cell clustering of ovarian Cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRβ pharmacological or genetic inhibition. In the absence of PDGFRβ, ovarian Cancer cells can be provided with fibronectin by cancer-associated fibroblasts (CAFs) to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients. This article is protected by copyright. All rights reserved.

Keywords

HGSOC; PDGFRβ; fibronectin; metastasis; ovarian cancer; tumorspheres.

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