Intratumoral oxygen gradients mediate sarcoma cell invasion

Significance Previous works demonstrated the role of hypoxia in tumor development and metastasis. However, the understanding how oxygen (O 2 ) gradients regulate early stages of tumor metastasis is lacking. Leveraging our O 2 -controlling hydrogel, we generated a 3D in vitro model that enables us to analyze cancer cell responses to O 2 gradients and small-molecule inhibitors. Using this approach, we present a previously unidentified concept in which O 2 acts as a 3D physicotactic agent during sarcoma tumor invasion, findings that are important for the understanding of the metastatic process. Through this concept, we also establish the 3D in vitro model as a platform for testing therapeutic targets and interventions for the treatment of sarcoma and potentially other cancers.