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

iScience (Sep 2024)

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

Journal volume & issue: Vol. 27, no. 9
p. 110635

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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