The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

Corre, Isabelle; Verrecchia, Franck; Crenn, Vincent; Rédini, Françoise; Trichet, Valérie

doi:10.3390/cells9040976

Cited by 308 publications

(291 citation statements)

References 163 publications

(206 reference statements)

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“…Tumorigenesis and cancer progression is supported by crosstalk-signaling between OS cells and the surrounding TME, being mainly composed of stromal cells, immune cells, endothelial cells and bone cells [ 40 ]. The immune component of OS TME is predominantly represented by the presence of tumor-associated macrophages (TAMs) that may act to impede or enhance the development and progression of tumor ( Figure 1 ).…”

Section: Osteosarcoma and Macrophage Functionmentioning

confidence: 99%

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Cersosimo

Lonardi

Bernardini

et al. 2020

IJMS

163

116

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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.

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Section: Osteosarcoma and Macrophage Functionmentioning

confidence: 99%

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Cersosimo

Lonardi

Bernardini

et al. 2020

IJMS

163

116

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“…However, the survival rate of patients is unsatisfactory because of potential chemoresistance, lung metastasis, or tumor relapses. Recently, increasing studies have explored new therapeutic strategies for OS such as the molecular target therapy ( Corre et al, 2020 ).…”

Section: Roles Of M 6 a In Musculoskeletal Disordementioning

confidence: 99%

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Zhang

Liu

et al. 2020

Front. Cell Dev. Biol.

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RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N 6 -methyladenosine (m 6 A) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of m 6 A in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between m 6 A modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of m 6 A modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of m 6 A in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.

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“…Multiple cytokines, growth factors, chemokines as well as their receptors have been reported as significant for OS cells' proliferation. In autocrine and paracrine mode these molecules stimulate cell division and differentiation of cells including not only OS cells, but also MSCs, osteoblasts and endothelial cells [139]. In OS intratumoral interleukin 6 (IL-6), interleukin 8 (IL-8), stromal derived factor 1 SDF-1 (known also as C-X-C motif chemokine 12-CXCL12), chemokines (C-C motif) ligand 5 (CCL5) and vascular endothelial growth factor (VEGF) promote OS cell growth and angiogenesis in the tumor, as well as metastatic spread [140,141].…”

Section: Role Of Cell-cell Interactions In Osteosarcomamentioning

confidence: 99%

Molecular Biology of Osteosarcoma

Czarnecka

Synoradzki

Firlej

et al. 2020

Cancers

240

186

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Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.

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The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

Cited by 308 publications

References 163 publications

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Molecular Biology of Osteosarcoma

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