Ovarian cancer relies on the PDGFRß-fibronectin axis for tumorsphere formation and metastatic spread.
Mol Oncol
; 18(1): 136-155, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-38010623
ABSTRACT
High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological 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 (PDGFRß) 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 PDGFRß pharmacological or genetic inhibition. In the absence of PDGFRß, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Cancer-Associated Fibroblasts
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Oncol
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
Spain
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA