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Osteosarcoma: Current Advances from Molecular and Cellular Mechanisms to Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 4210

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Special Issue Editors

Dr. Virinder Kaur Sarhadi

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Guest Editor

Department of Oral and Maxillofacial Diseases, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland
Interests: cancer; molecular genetics; osteosarcoma; cancer biomarkers

Dr. Francesca Perut

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Guest Editor

Biomedical Science and Technologies and Nanobiotechnology Lab, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
Interests: bone cell biology and oncology; bone tissue engineering and regenerative medicine; exosome-mediated communication in bone pathophysiology

Special Issue Information

Dear Colleagues,

Osteosarcoma is a rare aggressive primary bone cancer with the highest incidence in children and young adults between 10 and 30 years of age. Standard treatment for osteosarcoma is surgery and neoadjuvant/adjuvant chemotherapy, which is quite effective in localized disease. The prognosis for recurrent or metastatic osteosarcoma is poor and treatment may include targeted therapies with kinase inhibitors or mTOR inhibitors.

Osteosarcoma arises from mesenchymal-stem-cell-derived osteoblast precursor cells. The tumors are highly heterogeneous with complex genomic landscape involving numerous structural and copy number alterations. Alterations in TP53 are the most frequently somatic changes, while pathogenic germline mutations in RB1, TP53, RECQL4, BLM, and WRN are associated with an increased risk of osteosarcoma. Tumor heterogeneity and a lack of recurrent driver mutations make it difficult to identify effective molecularly targeted therapies. Recent multi-omics studies have enhanced our understanding of the molecular pathways in osteosarcoma pathogenesis and are opening up new opportunities for biomarker-driven precision therapies based on molecular subtypes or altered genomic or cellular pathways such as PI3K-ATK-mTOR signaling, homologous recombination repair pathway, or therapies based on the immune profile/response of tumors. This Special Issue will compile recent research on various cellular and molecular processes involved in osteosarcoma growth, progression, and drug sensitivity/resistance, which could lead to the identification of new drug targets or therapies and improvements in osteosarcoma treatment.

Dr. Virinder Kaur Sarhadi
Dr. Francesca Perut
Guest Editors

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 short 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

osteosarcoma
cell signalling
molecular pathways
transcriptome
epigenetics
genomics
drug targets
therapy
drug resistance
targeted therapy

Published Papers (3 papers)

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Research

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13 pages, 2716 KiB

Open AccessArticle

The Role of FAS Receptor Methylation in Osteosarcoma Metastasis

by Jiayi M. Sun, Wing-Yuk Chow, Gufeng Xu, M. John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M. Taylor, Alexander Yu, Jason E. Farrar, Donald A. Barkauskas, Richard Gorlick, Jaime M. Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C. Lau and on behalf of the TARGET Osteosarcoma Consortium

Int. J. Mol. Sci. 2023, 24(15), 12155; https://doi.org/10.3390/ijms241512155 - 29 Jul 2023

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Abstract

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of certain CpG sites that correlated significantly with FAS mRNA expression in a negative manner. Bisulfite sequencing revealed additional CpG sites, which were highly methylated in the metastatic LM7 cell line but unmethylated in its parental non-metastatic SaOS-2 cell line. Treatment with the demethylating agent, 5-azacytidine, resulted in a loss of methylation in CpG sites located within the FAS promoter and restored FAS protein expression in LM7 cells, resulting in reduced migration. Orthotopic implantation of 5-azacytidine treated LM7 cells into severe combined immunodeficient mice led to decreased lung metastases. These results suggest that DNA methylation of CGI shore sites may regulate FAS expression and constitute a potential target for osteosarcoma therapy, utilizing demethylating agents currently approved for the treatment of other cancers. Full article

(This article belongs to the Special Issue Osteosarcoma: Current Advances from Molecular and Cellular Mechanisms to Therapy)

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19 pages, 9639 KiB

Open AccessArticle

Gold Nanoparticles Inhibit Extravasation of Canine Osteosarcoma Cells in the Ex Ovo Chicken Embryo Chorioallantoic Membrane Model

by Anna Małek, Marek Wojnicki, Aleksandra Borkowska, Michał Wójcik, Gabriela Ziółek, Roman Lechowski and Katarzyna Zabielska-Koczywąs

Int. J. Mol. Sci. 2023, 24(12), 9858; https://doi.org/10.3390/ijms24129858 - 7 Jun 2023

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Abstract

Canine osteosarcoma (OS) is an aggressive bone tumor with high metastatic potential and poor prognosis, mainly due to metastatic disease. Nanomedicine-based agents can be used to improve both primary and metastatic tumor treatment. Recently, gold nanoparticles were shown to inhibit different stages of the metastatic cascade in various human cancers. Here, we assessed the potential inhibitory effect of the glutathione-stabilized gold nanoparticles (Au-GSH NPs) on canine OS cells extravasation, utilizing the ex ovo chick embryo chorioallantoic membrane (CAM) model. The calculation of cells extravasation rates was performed using wide-field fluorescent microscopy. Transmission electron microscopy and Microwave Plasma Atomic Emission Spectroscopy revealed Au-GSH NPs absorption by OS cells. We demonstrated that Au-GSH NPs are non-toxic and significantly inhibit canine OS cells extravasation rates, regardless of their aggressiveness phenotype. The results indicate that Au-GSH NPs can act as a possible anti metastatic agent for OS treatment. Furthermore, the implemented CAM model may be used as a valuable preclinical platform in veterinary medicine, such as testing anti-metastatic agents. Full article

(This article belongs to the Special Issue Osteosarcoma: Current Advances from Molecular and Cellular Mechanisms to Therapy)

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Review

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29 pages, 1205 KiB

Open AccessReview

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma

by Suzana Borović Šunjić, Morana Jaganjac, Josipa Vlainić, Mirna Halasz and Neven Žarković

Int. J. Mol. Sci. 2024, 25(8), 4559; https://doi.org/10.3390/ijms25084559 - 22 Apr 2024

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Abstract

Oxidative stress and lipid peroxidation play important roles in numerous physiological and pathological processes, while the bioactive products of lipid peroxidation, lipid hydroperoxides and reactive aldehydes, act as important mediators of redox signaling in normal and malignant cells. Many types of cancer, including osteosarcoma, express altered redox signaling pathways. Such redox signaling pathways protect cancer cells from the cytotoxic effects of oxidative stress, thus supporting malignant transformation, and eventually from cytotoxic anticancer therapies associated with oxidative stress. In this review, we aim to explore the status of lipid peroxidation in osteosarcoma and highlight the involvement of lipid peroxidation products in redox signaling pathways, including the involvement of lipid peroxidation in osteosarcoma therapies. Full article

(This article belongs to the Special Issue Osteosarcoma: Current Advances from Molecular and Cellular Mechanisms to Therapy)

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