Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.600980
Keywords
rhabdomyosarcoma; cancer-associated fibroblasts; tumor microenvironment; extracellular matrix proteins; stroma
Categories
Funding
- Progetto di Ateneo 2016 (Budget Integrato per la Ricerca dei Dipartimenti), Padova University
- Assocazione Puzzle, Padova, Italy
- University of Padova [GRIC15AIPF]
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The study demonstrates that unlike epithelial cancers, rhabdomyosarcoma (RMS) cells play a direct role in remodeling their own ECM and are less dependent on support from cancer-associated fibroblasts (CAFs). In both 2D and 3D models, the rate of interaction between RMS cells and fibroblasts is significantly lower, indicating a reduced reliance on CAFs for tumor growth.
Background The interplay between neoplastic cells and surrounding extracellular matrix (ECM) is one of the determinant elements for cancer growth. The remodeling of the ECM by cancer-associated fibroblasts (CAFs) shapes tumor microenvironment by depositing and digesting ECM proteins, hence promoting tumor growth and invasion. While for epithelial tumors CAFs are well characterized, little is known about the stroma composition of mesenchymal cancers, such as in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma during childhood and adolescence. The aim of this work is to identify the importance of CAFs in specifying RMS microenvironment and the role of these stromal cells in RMS growth. Methods We assessed in two dimensional (2D) and three dimensional (3D) systems the attraction between RMS cells and fibroblasts using epithelial colon cancer cell line as control. CAFs were studied in a xenogeneic mouse model of both tumor types and characterized in terms of fibroblast activation protein (FAP), mouse PDGFR expression, metalloproteases activation, and ECM gene and protein expression profiling. Results In 2D model, the rate of interaction between stromal and malignant cells was significantly lower in RMS with respect to colon cancer. Particularly, in 3D system, RMS spheroids tended to dismantle the compact aggregate when grown on the layer of stromal cells. In vivo, despite the well-formed tumor mass, murine CAFs were found in low percentage in RMS xenogeneic samples. Conclusions Our findings support the evidence that, differently from epithelial cancers, RMS cells are directly involved in their own ECM remodeling, and less dependent on CAFs support for cancer cell growth.
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