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International Journal of Molecular... Sep 2020The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone... (Review)
Review
The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.
Topics: Animals; Bone Neoplasms; Humans; Neoplasm Metastasis; Osteosarcoma; Signal Transduction; Tumor Microenvironment
PubMed: 32977425
DOI: 10.3390/ijms21196985 -
Annals of Oncology : Official Journal... Oct 2010The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical... (Review)
Review
The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical oncologists, surgeons, pathologists and radiologists. Therefore, therapy should be performed in specialized centers able to provide access to the full spectrum of care. As in other rare malignancies, treatment should be administered within prospective multicenter trials. Therapy must include complete surgical removal of all detectable tumor sites as well as multiagent chemotherapy. The chemotherapy regimen should include several or all of the following four drugs: doxorubicin, high-dose methotrexate with leukovorin-rescue, cisplatin and ifosfamide. Preoperative (neoadjuvant) plus postoperative (adjuvant) polychemotherapy should be preferred, because it allows preparation for safe surgery and preparation of the appropriate prosthesis for the individual patient. The choice of the postponed definitive surgical procedure should be influenced by the anatomical site of the primary tumor, its relationship to neighboring structures, such as vessels and nerves, age and growth potential of the patient, and probably also by the response of the tumor to preoperative chemotherapy. A major, as yet unsolved, problem is the dismal prognosis for patients with unresectable or relapsed osteosarcomas. Novel approaches are needed in order to improve their prognosis.
Topics: Bone Neoplasms; Combined Modality Therapy; Humans; Neoplasm Metastasis; Neoplasm Staging; Osteosarcoma; Prognosis; Recurrence
PubMed: 20943636
DOI: 10.1093/annonc/mdq276 -
British Journal of Pharmacology Jan 2022Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is... (Review)
Review
Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is highly predisposed in Paget's disease of the bone, and both have common characteristic skeletal features due to rapid bone remodelling. Osteosarcoma prognosis is location dependent, which further emphasizes the likely contribution of the bone microenvironment in its pathogenesis. Mechanobiology describes the processes involved when mechanical cues from the changing physical microenvironment of the bone are transduced to biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies have been used to curb tumour progression by direct alteration of the physical microenvironment or inhibition of metastasis-associated mechanosensitive proteins. This review emphasizes the contribution of mechanobiology to the progression of osteosarcoma and sheds light on current mechanobiology-based therapies and potential new targets for improving disease management. Additionally, the many different 3D models currently used to study osteosarcoma mechanobiology are summarized.
Topics: Biophysics; Bone Neoplasms; Humans; Osteitis Deformans; Osteosarcoma; Tumor Microenvironment
PubMed: 34679192
DOI: 10.1111/bph.15713 -
American Family Physician Aug 2018Primary bone cancers include osteosarcoma, Ewing sarcoma, and chondrosarcoma. They account for less than 1% of diagnosed cancers each year and are associated with... (Review)
Review
Primary bone cancers include osteosarcoma, Ewing sarcoma, and chondrosarcoma. They account for less than 1% of diagnosed cancers each year and are associated with significant morbidity and mortality. Timely diagnosis is challenging because of late patient presentation, nonspecific symptoms that mimic common musculoskeletal injuries, and low suspicion by physicians. Plain radiography is the preferred diagnostic test. Radiographic suspicion of a bone malignancy should prompt quick referral to a cancer center for multidisciplinary care. Osteosarcoma, the most common bone cancer, most often occurs in children and adolescents. It typically develops in the metaphysis of long bones, specifically the distal femur, proximal tibia, and proximal humerus. Metastasis to the lungs is common. Use of neoadjuvant and adjuvant chemotherapy, in combination with surgery, has improved survival rates to nearly 80% for patients with localized disease, and 90% to 95% of patients do not require limb amputation. Ewing sarcoma is the second most common bone cancer and is similar to osteosarcoma in terms of presenting symptoms, age at occurrence, and treatment. Prognosis for osteosarcoma and Ewing sarcoma depends on the presence of metastasis, which lowers the five-year survival rate to 20% to 30%. Chondrosarcoma is the rarest bone cancer, primarily affecting adults older than 40 years. Survival rates are higher because most of these tumors are low-grade lesions.
Topics: Age Factors; Bone Neoplasms; Chondrosarcoma; Early Detection of Cancer; Humans; Neoplasm Staging; Osteosarcoma; Patient Care Management; Patient Selection; Prognosis; Sarcoma, Ewing
PubMed: 30215968
DOI: No ID Found -
Cells Apr 2020Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly... (Review)
Review
Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.
Topics: Animals; Bone Remodeling; Humans; Immune System; Mesenchymal Stem Cells; Molecular Targeted Therapy; Osteosarcoma; Tumor Microenvironment
PubMed: 32326444
DOI: 10.3390/cells9040976 -
International Journal of Molecular... Jul 2020Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after... (Review)
Review
Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.
Topics: Bone Neoplasms; Humans; Neoplasm Metastasis; Osteosarcoma; Signal Transduction; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 32717819
DOI: 10.3390/ijms21155207 -
Frontiers in Immunology 2022Dysregulation of immune cell infiltration in the tumor microenvironment contributes to the progression of osteosarcoma (OS). In the present study, we explored genes...
Dysregulation of immune cell infiltration in the tumor microenvironment contributes to the progression of osteosarcoma (OS). In the present study, we explored genes related to immune cell infiltration and constructed a risk model to predict the prognosis of and guide therapeutic strategies for OS. The gene expression profile of OS was obtained from TARGET and Gene Expression Omnibus, which were set as the discovery and verification cohorts. CIBERSORT and Kaplan survival analyses were used to analyze the effects of immune cells on the overall survival rates of OS in the discovery cohort. Differentially expressed gene (DEG) analysis and protein-protein interaction (PPI) networks were used to analyze genes associated with immune cell infiltration. Cox regression analysis was used to select key genes to construct a risk model that classified OS tissues into high- and low-risk groups. The prognostic value of the risk model for survival and metastasis was analyzed by Kaplan-Meier survival analyses, receiver operating characteristic curves, and immunohistochemical experiments. Immunological characteristics and response effects of immune checkpoint blockade (ICB) therapy in OS tissues were analyzed using the ESTIMATE and Tumor Immune Dysfunction and Exclusion algorithms, while sensitivity for both targeted and chemotherapy drugs was analyzed using the OncoPredict algorithm. It was demonstrated that the high infiltration of resting dendritic cells in OS tissues was associated with poor prognosis. A total of 225 DEGs were found between the high- and low-infiltration groups of OS tissues, while 94 genes interacted with others. Through COX analyses, among these 94 genes, four genes (including AOC3, CDK6, COL22A1, and RNASE6) were used to construct a risk model. This risk model showed a remarkable prognostic value for survival rates and metastasis in both the discovery and verification cohorts. Even though a high microsatellite instability score was observed in the high-risk group, the ICB response in the high-risk group was poor. Furthermore, using OncoPredict, we found that the high-risk group OS tissues were resistant to seven drugs and sensitive to 25 drugs. Therefore, our study indicates that the resting dendritic cell signature constructed by AOC3, CDK6, COL22A1, and RNASE6 may contribute to predicting osteosarcoma prognosis and thus therapy guidance.
Topics: Bone Neoplasms; Gene Expression Profiling; Humans; Immune Checkpoint Inhibitors; Osteosarcoma; Prognosis; Tumor Microenvironment
PubMed: 36189307
DOI: 10.3389/fimmu.2022.1017120 -
Journal of Biomedical Science Apr 2023The tumor microenvironment (TME) has a central role in the oncogenesis of osteosarcomas. The composition of the TME is essential for the interaction between tumor and...
BACKGROUND
The tumor microenvironment (TME) has a central role in the oncogenesis of osteosarcomas. The composition of the TME is essential for the interaction between tumor and immune cells. The aim of this study was to establish a prognostic index (TMEindex) for osteosarcoma based on the TME, from which estimates about patient survival and individual response to immune checkpoint inhibitor (ICI) therapy can be deduced.
METHODS
Based on osteosarcoma samples from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, the ESTIMATE algorithm was used to estimate ImmuneScore and StromalScore. Combined differentially expressed gene analysis, weighted gene co-expression network analyses, the Least Absolute Shrinkage and Selection Operator regression and stepwise regression to construct the TMEindex. The prognostic role of TMEindex was validated in three independent datasets. The molecular and immune characteristics of TMEindex and the impact on immunotherapy were then comprehensively investigated. The expression of TMEindex genes in different cell types and its effects on osteosarcoma cells were explored by scRNA-Seq analysis and molecular biology experiments.
RESULTS
Fundamental is the expression of MYC, P4HA1, RAMP1 and TAC4. Patients with high TMEindex had worse overall survival, recurrence-free survival, and metastasis-free survival. TMEindex is an independent prognostic factor in osteosarcoma. TMEindex genes were mainly expressed in malignant cells. The knockdown of MYC and P4HA1 significantly inhibited the proliferation, invasion and migration of osteosarcoma cells. A high TME index is related to the MYC, mTOR, and DNA replication-related pathways. In contrast, a low TME index is related to immune-related signaling pathways such as the inflammatory response. The TMEindex was negatively correlated with ImmuneScore, StromalScore, immune cell infiltration, and various immune-related signature scores. Patients with a higher TMEindex had an immune-cold TME and higher invasiveness. Patients with a low TME index were more likely to respond to ICI therapy and achieve clinical benefit. In addition, the TME index correlated with response to 29 oncologic drugs.
CONCLUSIONS
The TMEindex is a promising biomarker to predict the prognosis of patients with osteosarcoma and their response to ICI therapy, and to distinguish the molecular and immune characteristics.
Topics: Humans; Prognosis; Tumor Microenvironment; Osteosarcoma; Algorithms; Bone Neoplasms
PubMed: 37055822
DOI: 10.1186/s12929-023-00917-3 -
Archives of Pathology & Laboratory... May 2012Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. Telangiectatic osteosarcoma is an unusual variant of osteosarcoma,... (Review)
Review
Osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. Telangiectatic osteosarcoma is an unusual variant of osteosarcoma, forming 3% to 10% of all osteosarcomas. Radiographically, these tumors appear as purely lytic destructive lesions located in the metaphyses of long bones. The location and x-ray appearance of telangiectatic osteosarcomas are reminiscent of an aneurysmal bone cyst and can test the acumen of a diagnostic radiologist. Distinguishing between the two entities microscopically can also be quite challenging. Telangiectatic osteosarcoma shows dilated blood-filled spaces lined or traversed by septa containing atypical stromal cells, with or without production of a lacelike osteoid matrix. This review highlights the diagnostic features of telangiectatic osteosarcoma and discusses differential diagnostic considerations, treatment options, and prognostic implications.
Topics: Adolescent; Bone Neoplasms; Child; Female; Humans; Male; Osteosarcoma; Telangiectasis; Young Adult
PubMed: 22540307
DOI: 10.5858/arpa.2011-0204-RS -
Anticancer Research 2004Osteosarcomas are malignant bone tumors consisting of cells with abnormal cellular functions. Although osteosarcoma-derived cells are commonly used for osteoblastic... (Comparative Study)
Comparative Study
BACKGROUND
Osteosarcomas are malignant bone tumors consisting of cells with abnormal cellular functions. Although osteosarcoma-derived cells are commonly used for osteoblastic models, the molecular composition of the osteosarcoma extracellular matrix (ECM) is not well characterized.
MATERIALS AND METHODS
We compared three osteosarcoma cell lines (MG-63, Saos-2 and U-2 OS) with normal human osteoblasts by immunocytochemistry. Cellular characteristics were assessed by morphometric analysis and proliferation kinetics.
RESULTS
All investigated osteosarcoma cell lines exhibited very heterogeneous labelling profiles and each differed significantly from that of normal osteoblasts. Saos-2 cells revealed the most mature osteoblastic labelling profile while U-2 OS cells were negative for most of the investigated osteoblastic markers.
CONCLUSION
We conclude that each osteosarcoma cell line exhibits a characteristic labelling profile and thus produces a differently composed extracellular matrix. This can be used in attempts to better characterize osteosarcoma, a as well as for their diagnosis.
Topics: Aged; Alkaline Phosphatase; Bone Neoplasms; Bone and Bones; Cell Growth Processes; Cell Line, Tumor; Female; Humans; Immunohistochemistry; Middle Aged; Osteoblasts; Osteosarcoma
PubMed: 15736406
DOI: No ID Found