The Etiology of Osteosarcoma

Ottaviani, Giulia; Jaffe, Norman

doi:10.1007/978-1-4419-0284-9_2

Cited by 192 publications

(173 citation statements)

References 55 publications

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“…Osteosarcoma can be caused by other types of cancer, including Li-Fraumeni syndrome (resulting from a p53 mutation), hereditary retinoblastoma (RB) and associated diseases caused by an RB mutation (13). Other internal or external factors can also contribute to the disease development (6,14). In the present study, the pathogenesis of osteosarcoma, with regard to the expression of COX-2 and miRNA-143 and the association between them, was investigated.…”

Section: Discussionmentioning

confidence: 98%

“…At present, the exact mechanism of osteosarcoma pathogenesis is unclear. Certain studies have suggested that osteosarcoma can be induced by other types of cancer, as well as environmental stimuli to bone cells, such as toxins, viruses and radiation (5)(6)(7). In addition, disturbed hormone levels can increase the incidence of osteosarcoma, particularly in teenagers with excess hormone secretion (8).…”

Section: Introductionmentioning

confidence: 99%

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Expression and clinical significance of cyclooxygenase-2 and microRNA-143 in osteosarcoma

Fang

Zhang

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of cyclooxygenase-2 and microRNA-143 in osteosarcoma

Fang

Zhang

Wang

et al. 2015

Experimental and Therapeutic Medicine

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“…Osteosarcoma (OS) is the most frequent primary malignant bone tumor in children and young adolescents (1,2). The survival rates for OS have improved considerably since the introduction of multi-agent chemotherapy in the 1980s, with a 5-year overall survival rate of 60-65% for patients without metastasis (3), and have remained relatively constant for the past two decades (4,5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-497 suppresses osteosarcoma tumor growth in vitro and in vivo

Zheng

et al. 2016

Oncology Letters

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Abstract. It has been demonstrated that microRNA-497 (miR-497) acts as a tumor suppressor and is involved in tumor progression, development and metastasis in several types of cancer. However, little is known about the exact role of miR-497 in osteosarcoma (OS). The aim of the current study was to investigate the potential role of miR-497 in human OS. The role of miR-497 in the growth and survival of OS cells was determined using several in vitro approaches and a nude mouse model. The results demonstrated that exogenous expression of miR-497 in human OS MG63 cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell arrest at the G0/G1 phase of the cell cycle. In addition, the results of the in vivo study indicated that restoration of miR-497 inhibited OS tumor growth in a nude mouse model. Overall, the results of the present study identified a crucial tumor suppressive role of miR-497 in the progression of OS, and suggested that miR-497 may be a potential therapeutic agent for the treatment of OS. IntroductionOsteosarcoma (OS) is the most frequent primary malignant bone tumor in children and young adolescents (1,2). The survival rates for OS have improved considerably since the introduction of multi-agent chemotherapy in the 1980s, with a 5-year overall survival rate of 60-65% for patients without metastasis (3), and have remained relatively constant for the past two decades (4,5). The development of conventional OS is a multistep process characterized by genetic and epigenetic alterations that affect key cellular pathways involved in cell growth and development (6). Therefore, an improved understanding of the molecular mechanisms involved in OS initiation and progression may contribute to the identification of a therapeutic target for the treatment of OS, which may additionally improve the overall outcome of patients with OS.MicroRNAs (miRNAs) are a family of small non-coding RNAs (19-25 nucleotides long), which are involved in the regulation of gene expression by inducing messenger (m)RNA degradation or repressing mRNA translation (7). miRNAs have been demonstrated to be involved in numerous physiological processes, including cell growth, apoptosis, development and tumorigenesis (7-12). miRNAs may act as oncogenes or tumor suppressors in the regulation of carcinogenesis, metastasis and drug resistance (10), and are considered to be biomarkers for the diagnosis of various types of cancer and potential novel targets for anticancer therapies (13).miRNA-497 (miR-497), an important member of the miR-15/16/195/424/497 family of miRNAs (14), is downregulated in various types of cancer, including ovarian (15), breast (16), colorectal (17) and cervical cancer (18). Previous studies have demonstrated that miR-497 exerts a tumor suppressor function in human colorectal cancer (17), cervical cancer (18), breast carcinoma (16), neuroblastoma (19), gastric cancer (20) and ovarian cancer (15,21). In addition, miR-497 has been observed to be downregulated in OS cell lines...

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“…Numerous studies have sought to improve our understanding of osteosarcoma, and epidemiological studies have reported significant findings, such as the effects of puberty, disorders of bone growth and remodeling, and genetic predisposition (2)(3)(4). However, as with several types of cancer, the etiology of osteosarcoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression

Liu

Guo

et al. 2012

Oncology Reports

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Abstract. It has been reported that overexpression of Mad2 in transgenic mice leads to a wide variety of tumors, and Mad2 overexpression causes lung tumor relapse after oncogene withdrawal. In a previous study we demonstrated that Mad2 is abnormally upregulated in human osteosarcoma, however, the underlying mechanisms remain unknown. In this study, we found that transient Mad2 overexpression is sufficient to cause early dyscrasia and decreased survival in a xenotransplantation osteosarcoma mouse model, and Mad2 overexpression is associated with increased invasiveness and pulmonary metastasis. We also found that upregulation of Mad2 was accompanied by enhanced capability to self-renew. Our data validate the correlation between upregulation of Mad2 and osteosarcoma advancement, and that the underlying mechanisms involve the increase of invasiveness and cancer stem cell properties. IntroductionOsteosarcoma is the most prevalent primary bone malignancy, and incidence peaks during the adolescent growth spurt (1). Numerous studies have sought to improve our understanding of osteosarcoma, and epidemiological studies have reported significant findings, such as the effects of puberty, disorders of bone growth and remodeling, and genetic predisposition (2-4). However, as with several types of cancer, the etiology of osteosarcoma remains unclear. Although neoadjuvant chemotherapy and limb salvage surgery greatly improve long-term survival and quality of life, recurrence and metastasis remain major challenges for clinicians.Spindle assembly checkpoint provides a surveillance mechanism responsible for the fidelity of mitotic chromosome segregation (5,6); it inhibits the onset of premature anaphase until all chromosomes are properly attached to the mitotic spindle apparatus and located at the metaphase plate, and defects in this process contribute to chromosomal instability and aneuploidy (5,7,8).Mad2 is a key component in the spindle assembly checkpoint (9). Our previous study demonstrated that Mad2 was overexpressed in human osteosarcoma tissue, and that increased expression of Mad2 was associated with early metastasis and poor survival (10). The findings of several reports are in accordance with our studies in many different malignant tumors (8,(11)(12)(13). The exact relationship between Mad2 expression and clinical outcome remains unclear.In this study, we found that Mad2 overexpression conferred osteosarcoma cells with an enhanced ability to cause early dyscrasia, promote pulmonary metastasis and decrease survival. The underlying mechanisms involve an increased invasiveness and enhanced cancer stem cell-like properties. Materials and methods Chemicals and reagents.The following antibodies for immunoblot and immunohistochemistry analysis were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA): Nanog, POU5F1, Sox2, ABCG2 and β-actin. We obtained primary antibody of Mad2, CXCR4, MMP-1 from Abcam (Cambridge, MA, USA), and the horseradish peroxidase-labeled goat anti-rabbit IgG (H+L) were obtained from Cell ...

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The Etiology of Osteosarcoma

Cited by 192 publications

References 55 publications

Expression and clinical significance of cyclooxygenase-2 and microRNA-143 in osteosarcoma

Expression and clinical significance of cyclooxygenase-2 and microRNA-143 in osteosarcoma

MicroRNA-497 suppresses osteosarcoma tumor growth in vitro and in vivo

Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression

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