A Technical Perspective: Understanding the Cellular Response to Hypoxia through In Vitro Model Systems White paper

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This white paper discusses the advantages and caveats associated with several sphere culture model systems currently used to evaluate cellular responses to hypoxia in cancer. 

Cellular response to hypoxia

Learn about key 3D cancer model systems for hypoxia research

  • Types of 3D cancer model systems used to evaluate the tumor microenvironment
  • Understanding hypoxia responses through 3D models
  • Advantages and caveats of key 3D cancer models
  • Small molecules as tools to modulate hypoxia


 Hypoxia plays a role in carcinogenesis directing a number of molecular pathways that generally promote tumor growth, invasiveness and metastasis. In vitro models of hypoxia present various challenges to approximate in vivo conditions including adequate regulation of oxygen levels and the duration of hypoxia. To better simulate the natural tumor microenvironment, investigators are increasingly relying on 3D culture models. Monolayer culture conditions tend to induce undesirable molecular and phenotypic cellular changes, whereas sphere models mimic the oxygen, nutrient and growth factor gradients in tumors in vivo. Moreover, 3D cultures may contain tumor as well as supporting non-tumor cells or stroma, allowing the study of cellular interactions as may occur in vivo. This review presents an overview of various sphere models, highlighting advantages and caveats for the use of current 3D culture systems to evaluate cellular responses to hypoxia in cancer.

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