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Cancers
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Osteosarcoma Microenvironment
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Osteosarcoma Microenvironment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 8994

Special Issue Editor

Dr. François Lamoureux

E-Mail Website
Guest Editor
Institut National de la Santé Et de la Recherche Médicale (INSERM), Universite De Nantes, F-44000 Nantes, France
Interests: bone tumors; osteosarcoma; bone tumor microenvironnment; tumor resistance; targeted therapies; metastases; cellular stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Osteosarcoma is the most common primary malignant bone tumor mainly affecting children and adolescents, accounting for 3% of pediatric cancers per year in the United States. The current treatment is combined neo-adjuvant chemotherapy and surgical resection with limb salvage in most cases. With these treatments, the survival rate is close to 70% for the localized forms or for the good responders to chemotherapy, but drastically drops to 25% for bad responders to chemotherapy or for patients with pulmonary metastasis at diagnosis. Moreover, patient survival has not increased in the last five decades, and the current therapeutic care remains unsatisfactory. This could be partially explained by the complex heterogeneity of osteosarcoma tumors without a clear genetic origin with identified driver mutation. Additionally, osteosarcoma develops and closely interacts with a complex microenvironment including bone cells, immune cells, as well as stromal and vascular cells supporting tumor growth and metastatic dissemination. A better knowledge of the osteosarcoma microenvironment is of interest to develop novel therapeutic approaches in osteosarcoma.

This Special Issue will provide a translational overview of fundamentals and recent advances of clinical research characterizing osteosarcoma bone microenvironment, new therapy development targeting the tumor microenvironment or covering the development of 3D models mimicking the osteosarcoma microenvironment.

Dr. François Lamoureux
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (3 papers)

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Research

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17 pages, 8034 KiB  
Article
Endogenous Extracellular Matrix Regulates the Response of Osteosarcoma 3D Spheroids to Doxorubicin
by Margherita Cortini, Francesca Macchi, Francesca Reggiani, Emanuele Vitale, Maria Veronica Lipreri, Francesca Perut, Alessia Ciarrocchi, Nicola Baldini and Sofia Avnet
Cancers 2023, 15(4), 1221; https://doi.org/10.3390/cancers15041221 - 14 Feb 2023
Cited by 13 | Viewed by 3173
Abstract
The extracellular matrix (ECM) modulates cell behavior, shape, and viability as well as mechanical properties. In recent years, ECM disregulation and aberrant remodeling has gained considerable attention in cancer targeting and prevention since it may stimulate tumorigenesis and metastasis. Here, we developed an [...] Read more.
The extracellular matrix (ECM) modulates cell behavior, shape, and viability as well as mechanical properties. In recent years, ECM disregulation and aberrant remodeling has gained considerable attention in cancer targeting and prevention since it may stimulate tumorigenesis and metastasis. Here, we developed an in vitro model that aims at mimicking the in vivo tumor microenvironment by recapitulating the interactions between osteosarcoma (OS) cells and ECM with respect to cancer progression. We long-term cultured 3D OS spheroids made of metastatic or non-metastatic OS cells mixed with mesenchymal stromal cells (MSCs); confirmed the deposition of ECM proteins such as Type I collagen, Type III collagen, and fibronectin by the stromal component at the interface between tumor cells and MSCs; and found that ECM secretion is inhibited by a neutralizing anti-IL-6 antibody, suggesting a new role of this cytokine in OS ECM deposition. Most importantly, we showed that the cytotoxic effect of doxorubicin is reduced by the presence of Type I collagen. We thus conclude that ECM protein deposition is crucial for modelling and studying drug response. Our results also suggest that targeting ECM proteins might improve the outcome of a subset of chemoresistant tumors. Full article
(This article belongs to the Special Issue Osteosarcoma Microenvironment)
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24 pages, 2306 KiB  
Article
Bio-Mechanical Model of Osteosarcoma Tumor Microenvironment: A Porous Media Approach
by Yu Hu, Navid Mohammad Mirzaei and Leili Shahriyari
Cancers 2022, 14(24), 6143; https://doi.org/10.3390/cancers14246143 - 13 Dec 2022
Cited by 4 | Viewed by 2271
Abstract
Osteosarcoma is the most common malignant bone tumor in children and adolescents with a poor prognosis. To describe the progression of osteosarcoma, we expanded a system of data-driven ODE from a previous study into a system of Reaction-Diffusion-Advection (RDA) equations and coupled it [...] Read more.
Osteosarcoma is the most common malignant bone tumor in children and adolescents with a poor prognosis. To describe the progression of osteosarcoma, we expanded a system of data-driven ODE from a previous study into a system of Reaction-Diffusion-Advection (RDA) equations and coupled it with Biot equations of poroelasticity to form a bio-mechanical model. The RDA system includes the spatio-temporal information of the key components of the tumor microenvironment. The Biot equations are comprised of an equation for the solid phase, which governs the movement of the solid tumor, and an equation for the fluid phase, which relates to the motion of cells. The model predicts the total number of cells and cytokines of the tumor microenvironment and simulates the tumor’s size growth. We simulated different scenarios using this model to investigate the impact of several biomedical settings on tumors’ growth. The results indicate the importance of macrophages in tumors’ growth. Particularly, we have observed a high co-localization of macrophages and cancer cells, and the concentration of tumor cells increases as the number of macrophages increases. Full article
(This article belongs to the Special Issue Osteosarcoma Microenvironment)
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Review

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24 pages, 1261 KiB  
Review
Decoding the Impact of Tumor Microenvironment in Osteosarcoma Progression and Metastasis
by Bikesh K. Nirala, Taku Yamamichi, D. Isabel Petrescu, Tasnuva N. Shafin and Jason T. Yustein
Cancers 2023, 15(20), 5108; https://doi.org/10.3390/cancers15205108 - 23 Oct 2023
Cited by 10 | Viewed by 2809
Abstract
Osteosarcoma (OS) is a heterogeneous, highly metastatic bone malignancy in children and adolescents. Despite advancements in multimodal treatment strategies, the prognosis for patients with metastatic or recurrent disease has not improved significantly in the last four decades. OS is a highly heterogeneous tumor; [...] Read more.
Osteosarcoma (OS) is a heterogeneous, highly metastatic bone malignancy in children and adolescents. Despite advancements in multimodal treatment strategies, the prognosis for patients with metastatic or recurrent disease has not improved significantly in the last four decades. OS is a highly heterogeneous tumor; its genetic background and the mechanism of oncogenesis are not well defined. Unfortunately, no effective molecular targeted therapy is currently available for this disease. Understanding osteosarcoma’s tumor microenvironment (TME) has recently gained much interest among scientists hoping to provide valuable insights into tumor heterogeneity, progression, metastasis, and the identification of novel therapeutic avenues. Here, we review the current understanding of the TME of OS, including different cellular and noncellular components, their crosstalk with OS tumor cells, and their involvement in tumor progression and metastasis. We also highlight past/current clinical trials targeting the TME of OS for effective therapies and potential future therapeutic strategies with negligible adverse effects. Full article
(This article belongs to the Special Issue Osteosarcoma Microenvironment)
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