Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment
- 1 October 2012
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Lab on a Chip
- Vol. 13 (2), 229-239
- https://doi.org/10.1039/c2lc40887b
Abstract
The reconstitution of a complex microenvironment on microfluidic chips is one of the cornerstones to demonstrate the improved flexibility of these devices with respect to macroscale in vitro approaches. In this work, we realised an on-chip model to investigate the interactions between cancer and immune system. To this end, we exploited mice deficient (Knock Out, KO) for interferon regulatory factor 8 (IRF-8), a transcription factor essential for the induction of competent immune responses, to investigate how IRF-8 gene expression contributes to regulate immune and melanoma cells crosstalk. In vivo, IRF-8 KO mice are highly permissive to B16 melanoma growth due to failure of immune cells to properly exert immunosurveillance. B16 cells and immune cells isolated from the spleen of wild type (WT) and IRF-8 KO mice were co-cultured for one week in a PDMS platform and monitored by fluorescence microscopy and time-lapse recordings. We observed that WT spleen cells migrated through microchannels connecting the culturing chambers towards B16 cells and tightly interacted with tumor cells, forming clusters of activation. In contrast, IRF-8 KO immune cells poorly interacted with melanoma cells. In parallel, B16 cells were more attracted towards microchannels, acquiring a more invasive behaviour in the presence of IRF-8 KO spleen cells, with respect to WT cells. Our results strongly confirm the in vivo observations and highlight the value of on-chip co-culture systems as a useful in vitro tool to elucidate the reciprocal interactions between cancer cells and host immune system, with relevant impact in the development of more effective anti-tumor therapeutic strategies.Keywords
This publication has 50 references indexed in Scilit:
- The physics of cancer: the role of physical interactions and mechanical forces in metastasisNature Reviews Cancer, 2011
- Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effectsIntegrative Biology, 2011
- Progress in understanding melanoma propagationMolecular Oncology, 2010
- Geometric cues for directing the differentiation of mesenchymal stem cellsProceedings of the National Academy of Sciences, 2010
- Chemokines and chemokine receptors: new insights into cancer-related inflammationTrends in Molecular Medicine, 2010
- Efficient tumour formation by single human melanoma cellsNature, 2008
- Isolation of rare circulating tumour cells in cancer patients by microchip technologyNature, 2007
- Role of chemokines in tumor growthCancer Letters, 2007
- In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitroNature Protocols, 2007
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002