Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment

Frontiers in Oncology
Franck Verrecchia, Françoise Rédini

Abstract

Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, and young adults. Despite encouraging progress in therapeutic management, including the advent of multidrug chemotherapy, the survival rates have remained unchanged for more than four decades: 75% at 5 years for localized disease, but two groups of patients are still at high risk: metastatic at diagnosis (overall survival around 40% at 5 years) and/or poor responders to chemotherapy (20% at 5 years). Because these tumors are classified as "complex genomic," it is extremely difficult to determine the signaling pathways that might be targeted by specific therapies. A hypothesis has thus emerged, stating that the particular microenvironment of these tumors may interfere with the tumor cells that promote chemoresistance and the dissemination of metastases. The stroma is composed of a large number of cell types (immune cells, endothelial cells, mesenchymal stromal cells, etc.) which secrete growth factors, such as transforming growth factor-β (TGF-β), which favors the development of primary tumors and dissemination of metastases by constituting a permissive niche at primary and distant sites. Rather than targeting the tumor cells...Continue Reading

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Jul 30, 2019·Immunological Reviews·Breelyn A Wilky
Feb 15, 2020·Tissue Engineering. Part B, Reviews·Eric R MolinaAntonios G Mikos
Apr 25, 2020·Cells·Isabelle CorreValérie Trichet
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Mar 30, 2021·Frontiers in Cell and Developmental Biology·Karin SchelchMichael Grusch
Jun 14, 2021·Research in Veterinary Science·Ana CarolinaSilveira RabeloMaria Angélica Miglino
Aug 8, 2021·International Journal of Molecular Sciences·Luca AmbrosioVincenzo Denaro
Oct 23, 2021·Biochemical Pharmacology·Mathilde MullardFranck Verrecchia

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Methods Mentioned

BETA
biopsies
xenograft

Clinical Trials Mentioned

NCT00356460
NCT00923169
NCT01472731
NCT01112293
NCT01401062
NCT02581787
NCT00844064
NCT00431561
NCT00761280
NCT00676507

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