EGFR-dependent aerotaxis is a common trait of breast tumour cells

Journal of Experimental & Clinical Cancer Research

Research

Ruth Rimokh¹  Rudy Gadet¹  Philippe Bertolino¹  Ivan Mikaelian¹  Anca Hennino¹  Germain Gillet¹  Philippe Gonzalo²  Mathieu Deygas³  Michel Péoc’h⁴  Sid-Ali Berremila⁴ 

[1] Centre de Recherche en Cancérologie de Lyon - Université Claude Bernard Lyon 1, UMR CNRS 5286, INSERM 1052, Centre Léon Bérard, 69373, Lyon, France;Centre de Recherche en Cancérologie de Lyon - Université Claude Bernard Lyon 1, UMR CNRS 5286, INSERM 1052, Centre Léon Bérard, 69373, Lyon, France;Biochemistry and Pharmacology department, UFR Medecine Saint-Etienne, CHU of Saint-Etienne, Saint-Etienne, France;Institut Curie, Paris Sciences et Lettres (PSL) Research University, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 144, Paris, France;Institut Pierre-Gilles de Gennes, PSL Research University, Paris, France;Pathology department, UFR Medecine Saint-Etienne, CHU of Saint-Etienne, Saint-Etienne, France;

关键词: Human breast cancer;    Breast epithelial cells;    aerotaxis;    EGFR;    Migration;    Invasion;    Hypoxia;    ROS;   

DOI  :  10.1186/s13046-022-02514-y

 received in 2022-07-26, accepted in 2022-10-04,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundAerotaxis, the chemotactism to oxygen, is well documented in prokaryotes. We previously reported for the first time that non-tumorigenic breast epithelial cells also display unequivocal directional migration towards oxygen. This process is independent of the hypoxia-inducible factor (HIF)/prolyl hydroxylase domain (PHD) pathway but controlled by the redox regulation of epidermal growth factor receptor (EGFR), with a reactive oxygen species (ROS) gradient overlapping the oxygen gradient at low oxygen concentration. Since hypoxia is an acknowledged hallmark of cancers, we addressed the putative contribution of aerotaxis to cancer metastasis by studying the directed migration of cancer cells from an hypoxic environment towards nearby oxygen sources, modelling the in vivo migration of cancer cells towards blood capillaries.MethodsWe subjected to the aerotactic test described in our previous papers cells isolated from fresh breast tumours analysed by the Pathology Department of the Saint-Etienne University Hospital (France) over a year. The main selection criterion, aside from patient consent, was the size of the tumour, which had to be large enough to perform the aerotactic tests without compromising routine diagnostic tests. Finally, we compared the aerotactic properties of these primary cells with those of commonly available breast cancer cell lines.ResultsWe show that cells freshly isolated from sixteen human breast tumour biopsies, representative of various histological characteristics and grades, are endowed with strong aerotactic properties similar to normal mammary epithelial cell lines. Strikingly, aerotaxis of these primary cancerous cells is also strongly dependent on both EGFR activation and ROS. In addition, we demonstrate that aerotaxis can trigger directional invasion of tumour cells within the extracellular matrix contrary to normal mammary epithelial cells. This contrasts with results obtained with breast cancer cell lines, in which aerotactic properties were either retained or impaired, and in some cases, even lost during the establishment of these cell lines.ConclusionsAltogether, our results support that aerotaxis may play an important role in breast tumour metastasis. In view of these findings, we discuss the prospects for combating metastatic spread.Trial registrationIRBN1462021/CHUSTE.Graphical abstract: EGFR-dependent aerotaxis of primary breast cancer cells

【 授权许可】

CC BY   
© The Author(s) 2022. corrected publication 2022

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