Tumor-on-a-chip models of the human microcirculatory system as a key tool for cancer metastasis research

Cancer is the second cause of death worldwide; however, most of the cancer-related deaths are not due to the primary tumour but to the metastasis. During cancer growth, there is an increase in the intratumoral pressure which is released by the lymphatic system. This activates genes that induce the chemotaxis of cancer cells towards lymphatic vessels promoting metastasis to lymph nodes and distant organs. As a result, and due to the critical role of the lymphatic system in cancer metastasis, cancer models including both blood and lymphatic vessels are needed.

Despite the huge range of cancer models available, in vitro ones fail to reproduce the complexity of the tumour microenvironment and in vivo animal models lack the immune system what affects cancer dissemination and the therapeutic response. As a result, tumour-on-a-chip (ToC) models, capable of recapitulating tissue-tissue interfaces as well as the in vivo microenvironment, emerge as a very attractive approach for studying cancer. Moreover, ToC models can mimic the hydrodynamic characteristics of the cancerous and normal microcirculatory system, formed by blood and lymphatic vessels. Herein, we review the latest advances in the field of ToC models of the human microcirculatory system.

Acknowledgements: FCT (2MATCH-PTDC/BTM-ORG/28070/2017; CEECIND/00352/2017); H2020-EU (FoReCaST-668983)