Bone marrow‐derived mesenchymal stem cells promote invasiveness and transendothelial migration of osteosarcoma cells via a mesenchymal to amoeboid transition

Autor: Angela Leo, Valentina Gori, L. Piccini, Maria Letizia Taddei, Matteo Lulli, Laura Pietrovito, Franco Bambi, Matteo Parri, Valentina Becherucci, Paola Chiarugi
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
transendothelial migration
Cancer Research
RHOA
Carcinogenesis
Neovascularization
Physiologic
Motility
Bone Marrow Cells
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Cancer-Associated Fibroblasts
Cell Line
Tumor
osteosarcoma
Human Umbilical Vein Endothelial Cells
Genetics
medicine
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Bone marrow-derived mesenchymal stem cells
cytokines
tumor plasticity
Research Articles
tumour plasticity
biology
Chemistry
Mesenchymal stem cell
Transendothelial and Transepithelial Migration
Interleukin
Mesenchymal Stem Cells
Chemotaxis
General Medicine
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Phenotype
030104 developmental biology
medicine.anatomical_structure
Oncology
Culture Media
Conditioned
030220 oncology & carcinogenesis
biology.protein
Cancer research
Intercellular Signaling Peptides and Proteins
Molecular Medicine
Osteosarcoma
bone marrow‐derived mesenchymal stem cells
Bone marrow
Research Article
Transforming growth factor
Zdroj: Molecular Oncology, Vol 12, Iss 5, Pp 659-676 (2018)
Molecular Oncology
ISSN: 1574-7891
1878-0261
Popis: There is growing evidence to suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are key players in tumour stroma. Here, we investigated the cross-talk between BM-MSCs and osteosarcoma (OS) cells. We revealed a strong tropism of BM-MSCs towards these tumour cells and identified monocyte chemoattractant protein (MCP)-1, growth-regulated oncogene (GRO)-α and transforming growth factor (TGF)-β1 as pivotal factors for BM-MSC chemotaxis. Once in contact with OS cells, BM-MSCs trans-differentiate into cancer-associated fibroblasts, further increasing MCP-1, GRO-α, interleukin (IL)-6 and IL-8 levels in the tumour microenvironment. These cytokines promote mesenchymal to amoeboid transition (MAT), driven by activation of the small GTPase RhoA, in OS cells, as illustrated by the in vitro assay and live imaging. The outcome is a significant increase of aggressiveness in OS cells in terms of motility, invasiveness and transendothelial migration. In keeping with their enhanced transendothelial migration abilities, OS cells stimulated by BM-MSCs also sustain migration, invasion and formation of the in vitro capillary network of endothelial cells. Thus, BM-MSC recruitment to the OS site and the consequent cytokine-induced MAT are crucial events in OS malignancy.
Databáze: OpenAIRE
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