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Review Open Access

Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review)

  • Authors:
    • Tao Shi
    • Jianping Kang
    • Qiyang Wang
    • Jiamei Song
    • Xiaofeng He
  • View Affiliations / Copyright

    Affiliations: Department of Pain, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China, Department of Orthopedic Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China, Department of Orthopedic Surgery, Yunnan Province Spinal Cord Disease Clinical Medical Center, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650000, P.R. China, Department of Reproductive Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 20
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    Published online on: November 4, 2025
       https://doi.org/10.3892/ol.2025.15373
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Abstract

Osteosarcoma (OS), a common primary malignant bone tumor in children and young adults, is significantly influenced by a complex tumor microenvironment (TME) that includes bone cells, stromal cells, vascular cells, immune cells and a mineralized extracellular matrix (ECM). In recent years, the role of the TME in OS progression has garnered increasing attention. The TME not only provides the physical and biochemical support necessary for tumor cell growth, invasion and metastasis, but also promotes the maintenance of the malignant tumor phenotype through mechanisms such as immune suppression, angiogenesis and metabolic reprogramming. The present review discusses how various cellular and non‑cellular components within the OS TME interact to drive tumor progression. Consequently, targeting the TME has emerged as a promising therapeutic strategy to overcome the limitations of conventional treatments, particularly for metastatic or recurrent OS. The present review underscores the potential of TME‑targeted therapies and highlights the need for further research into the heterogeneity of the TME to improve clinical outcomes.
View Figures

Figure 1

Microenvironment of osteosarcoma is
composed of cellular and non-cellular components, including bone
cells (osteoblasts, osteoclasts and osteocytes), stromal cells
(mesenchymal stem cells and fibroblasts), immune cells (bone marrow
and lymphocytes), mineralized ECM, rich microcirculation vessels
and a hypoxic environment. Other components include CTCs, EVs and
various signaling molecules. The tumor microenvironment not only
provides a favorable growth environment for tumor cells, but also
secretes various factors, including various cytokines, chemokines
and growth factors, promoting tumor cell metastasis. The figure was
created by BioRender. OSc, osteosarcoma cell; Ocytes, osteocyte;
OCs, osteoclast; OBs, osteoblast; TAMs, tumor-associated
macrophages; DCs, dendritic cells; MST, mesenchymal stem cell;
Lymph, lymphocyte; ECM, extracellular matrix; EV, exosomal
vesicles; BMC, bone marrow cell; NT, normal tissue; MSC,
multipotent stem cell; CTCs, circulating tumor cells.
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Copy and paste a formatted citation
Spandidos Publications style
Shi T, Kang J, Wang Q, Song J and He X: Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review). Oncol Lett 31: 20, 2026.
APA
Shi, T., Kang, J., Wang, Q., Song, J., & He, X. (2026). Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review). Oncology Letters, 31, 20. https://doi.org/10.3892/ol.2025.15373
MLA
Shi, T., Kang, J., Wang, Q., Song, J., He, X."Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review)". Oncology Letters 31.1 (2026): 20.
Chicago
Shi, T., Kang, J., Wang, Q., Song, J., He, X."Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review)". Oncology Letters 31, no. 1 (2026): 20. https://doi.org/10.3892/ol.2025.15373
Copy and paste a formatted citation
x
Spandidos Publications style
Shi T, Kang J, Wang Q, Song J and He X: Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review). Oncol Lett 31: 20, 2026.
APA
Shi, T., Kang, J., Wang, Q., Song, J., & He, X. (2026). Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review). Oncology Letters, 31, 20. https://doi.org/10.3892/ol.2025.15373
MLA
Shi, T., Kang, J., Wang, Q., Song, J., He, X."Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review)". Oncology Letters 31.1 (2026): 20.
Chicago
Shi, T., Kang, J., Wang, Q., Song, J., He, X."Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review)". Oncology Letters 31, no. 1 (2026): 20. https://doi.org/10.3892/ol.2025.15373
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