Cancer cell – Fibroblast crosstalk via HB-EGF, EGFR, and MAPK signaling promotes the expression of macrophage chemo-attractants in squamous cell carcinoma
Giovanni Giangreco,
Antonio Rullan,
Yutaka Naito,
Dhruva Biswas,
Yun-Hsin Liu,
Steven Hooper,
Pablo Nenclares,
Shreerang Bhide,
Maggie Chon U Cheang,
Probir Chakravarty,
Eishu Hirata,
Charles Swanton,
Alan Melcher,
Kevin Harrington,
Erik Sahai
Affiliations
Giovanni Giangreco
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Corresponding author
Antonio Rullan
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Yutaka Naito
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Dhruva Biswas
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, 72 Huntley Street, London WC1E 6DD, UK; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Bill Lyons Informatics Centre, University College London Cancer Institute, 72 Huntley Street, London WC1E 6DD, UK
Yun-Hsin Liu
Bioinformatics Platform, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Steven Hooper
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Pablo Nenclares
Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Shreerang Bhide
Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Maggie Chon U Cheang
Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Probir Chakravarty
Bioinformatics Platform, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Eishu Hirata
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Charles Swanton
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Bill Lyons Informatics Centre, University College London Cancer Institute, 72 Huntley Street, London WC1E 6DD, UK; Department of Oncology, University College London Hospitals, London, UK
Alan Melcher
Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Kevin Harrington
Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Head and Neck Unit, The Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, UK
Erik Sahai
Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Corresponding author
Summary: Interactions between cells in the tumor microenvironment (TME) shape cancer progression and patient prognosis. To gain insights into how the TME influences cancer outcomes, we derive gene expression signatures indicative of signaling between stromal fibroblasts and cancer cells, and demonstrate their prognostic significance in multiple and independent squamous cell carcinoma cohorts. By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MAPK axis represents a hub of tumor-stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages. Together, these analyses demonstrate the utility of our approach for interrogating the extent and consequences of TME crosstalk.
