Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Pathogenesis of Osteosarcoma
share announcement

Pathogenesis of Osteosarcoma

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 9905

Special Issue Editor

Dr. Takatsune Shimizu

E-Mail Website
Guest Editor
Department of Pathophysiology, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Interests: osteosarcoma; preclinical models of osteosarcoma; metastasis; tumor microenvironment; tumor immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteosarcoma is the most common primary malignant tumor of bone. Recent advances in combination therapy involving surgery and chemotherapy have dramatically improved prognosis. However, patients with advanced stages do not survive over the long term, which has remained unchanged over the past 30 years. To develop promising therapeutic options, we need to gather the knowledge about the molecular pathogenesis of osteosarcoma and translate them into clinical settings. Both cell intrinsic and environmental factors are undoubtedly and collectively involved in the onset and progression of osteosarcoma as well as the formation of tumor heterogeneity, leading to therapeutic resistance. Genetic and/or epigenetic abnormalities that could dysregulate oncogenes, tumor suppressors and intracellular signaling pathways are frequently observed in osteosarcoma. The complex tumor microenvironment of osteosarcoma including bone homeostasis and the immune response is currently receiving the most attention.

This Special Issue offers an Open Access forum that aims to bring together a collection of original research and review articles addressing the expanding field of the pathogenesis of osteosarcoma. We hope to provide a stimulating resource for the fascinating subject of osteosarcoma research.

Some suggested potential topics are genetic and/or epigenetic disorders, whose study may be based on comprehensive analyses such as genome-wide association studies; genomic instability, which may be caused by chromothripsis and kataegis; molecular disorders that promote tumor heterogeneity and disease progression; the disturbance of bone homeostasis; metabolic abnormalities in osteosarcoma; immunologic findings in osteosarcoma research; and new models for studying osteosarcoma.

Dr. Takatsune Shimizu
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 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. Cells 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 2700 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.

Keywords

  • osteosarcoma
  • metastasis tumor heterogeneity
  • genomic instability
  • cancer metabolism
  • bone homeostasis
  • tumor immunology

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

18 pages, 4092 KiB  
Article
Depletion of R270C Mutant p53 in Osteosarcoma Attenuates Cell Growth but Does Not Prevent Invasion and Metastasis In Vivo
by Takatsune Shimizu, Eiji Sugihara, Hideyuki Takeshima, Hiroyuki Nobusue, Rui Yamaguchi, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Toshikazu Ushijima, Akihiro Muto and Hideyuki Saya
Cells 2022, 11(22), 3614; https://doi.org/10.3390/cells11223614 - 15 Nov 2022
Cited by 1 | Viewed by 1749
Abstract
Novel therapeutic targets are needed to better treat osteosarcoma, which is the most common bone malignancy. We previously developed mouse osteosarcoma cells, designated AX (accelerated bone formation) cells from bone marrow stromal cells. AX cells harbor both wild-type and mutant forms of p53 [...] Read more.
Novel therapeutic targets are needed to better treat osteosarcoma, which is the most common bone malignancy. We previously developed mouse osteosarcoma cells, designated AX (accelerated bone formation) cells from bone marrow stromal cells. AX cells harbor both wild-type and mutant forms of p53 (R270C in the DNA-binding domain, which is equivalent to human R273C). In this study, we showed that mutant p53 did not suppress the transcriptional activation function of wild-type p53 in AX cells. Notably, AXT cells, which are cells derived from tumors originating from AX cells, lost wild-type p53 expression, were devoid of the intact transcription activation function, and were resistant to doxorubicin. ChIP-seq analyses revealed that this mutant form of p53 bound to chromatin in the vicinity of the transcription start sites of various genes but exhibited a different binding profile from wild-type p53. The knockout of mutant p53 in AX and AXT cells by CRISPR–Cas9 attenuated tumor growth but did not affect the invasion of these cells. In addition, depletion of mutant p53 did not prevent metastasis in vivo. Therefore, the therapeutic potency targeting R270C (equivalent to human R273C) mutant p53 is limited in osteosarcoma. However, considering the heterogeneous nature of osteosarcoma, it is important to further evaluate the biological and clinical significance of mutant p53 in various cases. Full article
(This article belongs to the Special Issue Pathogenesis of Osteosarcoma)
►▼ Show Figures

Figure 1

11 pages, 2048 KiB  
Article
Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells
by Yunmi Ko, Yeon Ho Jeong and Jun Ah Lee
Cells 2022, 11(14), 2164; https://doi.org/10.3390/cells11142164 - 11 Jul 2022
Cited by 3 | Viewed by 1653
Abstract
Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic [...] Read more.
Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3+γδTCR+Vγ9+ triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 μM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS. Full article
(This article belongs to the Special Issue Pathogenesis of Osteosarcoma)
►▼ Show Figures

Figure 1

9 pages, 1420 KiB  
Article
Osteosarcoma in Adolescents and Young Adults
by Jun Ah Lee, Jiwon Lim, Hye Young Jin, Meerim Park, Hyeon Jin Park, Jong Woong Park, June Hyuk Kim, Hyun Guy Kang and Young-Joo Won
Cells 2021, 10(10), 2684; https://doi.org/10.3390/cells10102684 - 07 Oct 2021
Cited by 13 | Viewed by 2619
Abstract
The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer [...] Read more.
The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer Registry. We compared survival trends and clinical characteristics between AYA and other age groups. AYA comprised 43.3% (1309/3022) of the osteosarcoma cases. Compared to other age groups, the male-to-female ratio was highest in AYA (1.61:1). The proportion of tumors located in an extremity was 80.3% in AYA, which was lower than in young children (92.5%) or pubertal children (93.8%) but higher than in adults (55.7%) or the elderly (47.5%). As for treatments, 71.2% of AYA received local treatment and systemic chemotherapy, and 28.8% received only local treatment (surgery: 261, radiotherapy: 9, surgery and radiotherapy: 5). The 5-year overall survival (OS) was lower in AYA (68%) than in young children (78%) or pubertal children (73%) but higher than in adults (47%) or the elderly (25%). When AYA were divided into five subgroups by age, patients aged 15–19 years constituted the largest proportion (45.4%, n = 594). Additionally, the proportion of patients with a non-extremity tumor increased in an age-dependent manner, from 10.3% in AYA aged 15–19 years to 35.3% in AYA aged 35–39 years. OS did not significantly differ among the different age subgroups of AYA. The clinical characteristics and OS of the AYA were more similar to those of children than to those of adults. There is a need for cooperation between pediatric and adult oncologists for effective osteosarcoma treatment in AYA. Full article
(This article belongs to the Special Issue Pathogenesis of Osteosarcoma)
►▼ Show Figures

Figure 1

20 pages, 7196 KiB  
Article
CK2α/CSNK2A1 Induces Resistance to Doxorubicin through SIRT6-Mediated Activation of the DNA Damage Repair Pathway
by Usama Khamis Hussein, Asmaa Gamal Ahmed, Yiping Song, Kyoung Min Kim, Young Jae Moon, Ae-Ri Ahn, Ho Sung Park, Su Jin Ahn, See-Hyoung Park, Jung Ryul Kim and Kyu Yun Jang
Cells 2021, 10(7), 1770; https://doi.org/10.3390/cells10071770 - 13 Jul 2021
Cited by 9 | Viewed by 3058
Abstract
CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved [...] Read more.
CK2α/CSNK2A1 is involved in cancer progression by phosphorylating various signaling molecules. Considering the role of CSNK2A1 in cancer progression and the phosphorylation of SIRT6 and the role of SIRT6 in chemoresistance through the DNA damage repair pathway, CSNK2A1 and SIRT6 might be involved in resistance to conventional anti-cancer therapies. We evaluated the expression of CSNK2A1 and phosphorylated SIRT6 in the 37 osteosarcoma patients and investigated the effects of CSNK2A1 and the phosphorylation of SIRT6 on Ser338 on resistance to the anti-cancer effects of doxorubicin. Higher expression of CSNK2A1 and phosphorylated SIRT6 was associated with shorter survival in osteosarcoma patients. U2OS and KHOS/NP osteosarcoma cells with induced overexpression of CSNK2A1 were resistant to the cytotoxic effects of doxorubicin, and the knock-down of CSNK2A1 potentiated the cytotoxic effects of doxorubicin. CSNK2A1 overexpression-mediated resistance to doxorubicin was associated with SIRT6 phosphorylation and the induction of the DNA damage repair pathway molecules. CSNK2A1- and SIRT6-mediated resistance to doxorubicin in vivo was attenuated via mutation of SIRT6 at the Ser338 phosphorylation site. Emodin, a CSNK2A1 inhibitor, potentiated the cytotoxic effects of doxorubicin in osteosarcoma cells. This study suggests that blocking the CSNK2A1-SIRT6-DNA damage repair pathway might be a new therapeutic stratagem for osteosarcomas. Full article
(This article belongs to the Special Issue Pathogenesis of Osteosarcoma)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop