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Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models

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Abstract 

Osteosarcoma (OS) is the most common primary bone cancer in children and young adults. This type of cancer is characterized by a high mortality rate, especially for patients with resistant lung metastases. Given its low incidence, high genetic heterogeneity, the lack of effective targets, and poor availability of relevant in vitro and in vivo models to study the tumor progression and the metastatic cascade, the pathophysiology of OS is still poorly understood and the translation of novel drugs into the market has become stagnant. Due to the importance of the tumor microenvironment (TME) in the development of metastases and the growing interest in targeting TME-specific pathways for novel therapeutics in cancer, models that closely represent these interactions are crucial for a better understanding of cancer-related events. In OS research, most studies rely on oversimplified two-dimensional (2D) assays and complex animal models that do not faithfully recapitulate OS development and progression. In turn, three-dimensional (3D) models are able to mimic not only the physical 3D environment in which cancer cells grow but also involve interactions with the TME, including its extracellular matrix, and thus are promising tools for drug screening studies. In this review, the existing and innovative OS in vitro 3D models are highlighted, focusing on how the TME is crucial to develop effective platforms for OS tumor and metastasis modeling in a physiologically relevant context.

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Acknowledgements

This paper was financed by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia.

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  1. Instituto de Investigação E Inovação Em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal

    João Rodrigues, Bruno Sarmento & Catarina Leite Pereira

  2. Instituto de Engenharia Biomédica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal

    João Rodrigues, Bruno Sarmento & Catarina Leite Pereira

  3. Instituto Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo 228, 4150-180, Porto, Portugal

    João Rodrigues

  4. Faculdade de Engenharia da Universidade Do Porto (FEUP), University of Porto, Rua Dr. Roberto Frias, 4200-465, Porto, Portugal

    João Rodrigues

  5. CESPU, Instituto de Investigação E Formação Avançada Em Ciências E Tecnologias da Saúde, Rua Central da Gandra 1317, 4585-116, Gandra, Portugal

    Bruno Sarmento

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  1. João Rodrigues
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Rodrigues, J., Sarmento, B. & Pereira, C.L. Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models. In vitro models 1, 5–27 (2022). https://doi.org/10.1007/s44164-022-00008-x

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