Cellular and Genetic Background of Osteosarcoma

Urlić, Inga; Jovičić, Marijana Šimić; Ostojić, Karla; Ivković, Alan

doi:10.3390/cimb45050276

Cited by 8 publications

(4 citation statements)

References 126 publications

(154 reference statements)

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“…Furthermore, the MSC-derived osteosarcoma cancer stem cells (O-CSC) can influence and promote tumorigenesis through intercellular communication and utility of growth factor containing vesicles, which, as a result, enhance recruitment of circulating MSCs that will aid in tumorigenesis [47]. The varying surrounding microenviroment acts as a supportive factor in further OS-CSC heterogeneity, where the exploitation of bone signaling allows the formation of niches (as illustrated by Abarrategi and colleagues in 2016) as the perivascular niche, the endosteal niche, and the hypoxic niche.…”

Section: Cancer Cell Populationsmentioning

confidence: 99%

“…Whole genomic sequencing in pediatric patients in 2020 revealed that additional aberrant genomic modifications, such as chromosomal structural alterations secondary to chromothripsis, occurred in 20-89% of the patients, and 50-85% of patients have presented with kataegis that further promotes disease heterogeneity in OS [50]. This contributed to the formation of OS subclasses varying in morphology, metabolism, tumor microenvironment, immunogenicity, and metastatic potential, thus posing a challenge in evaluating the initial cause of osteosarcoma carcinogenesis [47]. Furthermore, deficiencies in DNA damage surveillance and repair also contributed to chromosomal structural abnormalities, deregulation of the tumor suppressor function, and uncontrolled cell cycle [41,43,51].…”

Section: Genomic Naturementioning

confidence: 99%

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Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

Al-Ansari,

Samuel,

Büsselberg

2024

Biomolecules

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Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep–wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as inflammation. Additionally, melatonin has demonstrated promising potential as an anti-cancer agent as its function includes inhibition of tumorigenesis, induction of apoptosis, and regulation of anti-tumor immune response. Although a precise pathophysiological mechanism is yet to be established, several pathways related to the regulation of cell cycle progression, DNA repair mechanisms, and antioxidant activity have been implicated in the anti-neoplastic potential of melatonin. In the current manuscript, we focus on the potential anti-cancer properties of melatonin and its use in treating and managing pediatric osteosarcoma. This aggressive bone tumor primarily affects children and adolescents and is treated mainly by surgical and radio-oncological interventions, which has improved survival rates among affected individuals. Significant disadvantages to these interventions include disease recurrence, therapy-related toxicity, and severe/debilitating side effects that the patients have to endure, significantly affecting their quality of life. Melatonin has therapeutic effects when used for treating osteosarcoma, attributed to its ability to halt cancer cell proliferation and trigger apoptotic cell death, thereby enhancing chemotherapeutic efficacy. Furthermore, the antioxidative function of melatonin alleviates harmful side effects of chemotherapy-induced oxidative damage, aiding in decreasing therapeutic toxicities. The review concisely explains the many mechanisms by which melatonin targets osteosarcoma, as evidenced by significant results from several in vitro and animal models. Nevertheless, if further explored, human trials remain a challenge that could shed light and support its utility as an adjunctive therapeutic modality for treating osteosarcoma.

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Section: Cancer Cell Populationsmentioning

confidence: 99%

Section: Genomic Naturementioning

confidence: 99%

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

Al-Ansari,

Samuel,

Büsselberg

2024

Biomolecules

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“…OS is not a uniform mass of cancer cells, but a complex, organ-like structure with diverse cell types influenced by various environmental factors [ 14 , 15 ]. An individual with OS is subject to a multitude of complex biological, structural, mechanical, and soluble factors that may affect the effectiveness of potential therapeutics [ 7 ].…”

Section: Advance In Os Cells and Modelsmentioning

confidence: 99%

Advances of Osteosarcoma Models for Drug Discovery and Precision Medicine

Tan,

Wang,

et al. 2023

Biomolecules

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The management of osteosarcoma (OS) patients presents a significant clinical challenge. Despite progress in conventional and targeted therapies, the survival rate of OS patients remains limited largely due to therapy resistance and the high metastatic potential of the disease. OS models that accurately reflect the fundamental characteristics are vital to the innovation and validation of effective therapies. This review provides an insight into the advances and challenges in OS drug development, focusing on various preclinical models, including cell lines, 3D culture models, murine models, and canine models. The relevance, strengths, and limitations of each model in OS research are explored. In particular, we highlight a range of potential therapeutics identified through these models. These instances of successful drug development represent promising pathways for personalized OS treatment.

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“… 5 For recurrent diseases, surgical excision is superior to systemic therapy, while unresectable cases will be treated by systemic therapy or comprehensive therapy. 6 In addition, radiotherapy can help eliminate small or minimal residual tumors when substantial surgical resection is not feasible. 7 However, in most cases of osteosarcoma, radiotherapy is limited and its efficacy and indications are limited.…”

Section: Introductionmentioning

confidence: 99%

NEK6 Promotes the Progression of Osteosarcoma Through Activating STAT3 Signaling Pathway by Down-Regulation of miR-26a-5p

Zhu¹,

Sun²,

Xue³

et al. 2023

IJGM

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Background Osteosarcoma is a malignant tumor originating from the skeletal system. There is no effective treatment other than surgery and chemotherapy, which seriously endangers the health of children and adolescents. NEK6 is a novel discovered Serine/Threonine protein kinase that can regulate cell cycle and activate several oncogenic pathways. Methods NEK6 expression in pan-cancer including sarcoma was evaluated using analysis tools of TIMER, UALCNA and GEPIA with TCGA database, and its association with overall survival in patients with sarcoma was also analyzed. TargetScan, tarbase, microT-CDS and Starbase online software were used to predict NEK6-targeted miRNAs, including miR-26a-5p. Tumor tissues from patients with osteosarcoma were collected for NEK6 and miRNA detection using RT-qPCR. NEK6 down-regulated by siRNAs or miR-26a-5p in osteosarcoma cells was detected by RT-qPCR, Western blot and Immunofluorescence staining assays. Effects of NEK6 knockdown on proliferation, migration, invasion and apoptosis of osteosarcoma cells were detected by CCK-8, wound healing, transwell and flow cytometry, respectively. The expressions of STAT3, metastasis and apoptosis-related genes were detected by Western blot. Results High expression of NEK6 and low expression of miR-26a-5p were lowly expressed in osteosarcoma and they were negative correlation. NEK6 has been confirmed as a direct target for miR-26a-5p. In addition, NEK6 down-regulated by siRNAs or miR-26a-5p led to inhibition of cell proliferation, migration and invasion while promoting cell apoptosis. The levels of phosphorylated STAT3 and metastasis genes (MMP-2, MMP-9) were inhibited, while apoptotic gene Bax was promoted and Bcl2 was inhibited by miR-26a-5p upregulation. Conclusion NEK6 can promote osteosarcoma progression via activating STAT3 signaling pathway, which is inhibited by miR-26a-5p, suggesting that NEK6 is a potential oncogene and miR-26a-5p is a suppressor of osteosarcoma. The strategy of inhibiting of NEK6 by miR-26a-5p may be an effective approach for osteosarcoma therapy.

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Cellular and Genetic Background of Osteosarcoma

Cited by 8 publications

References 126 publications

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations

Advances of Osteosarcoma Models for Drug Discovery and Precision Medicine

NEK6 Promotes the Progression of Osteosarcoma Through Activating STAT3 Signaling Pathway by Down-Regulation of miR-26a-5p

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