[en] Oestrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of oestrogens in lung cancer development is a pre-requisite to support the development of sex-based treatments and identify patients who could potentially benefit from anti-oestrogen treatments. In this study, we highlight the contribution of lymphatic and blood endothelia in the sex-dependent modulation of lung cancer. The orthotopic graft of syngeneic lung cancer cells into immunocompetent mice showed that lung tumours grow faster in female mice than in males. Moreover, oestradiol (E2) promoted tumour development, increased lymph/angiogenesis and VEGFA and bFGF levels in lung tumours of females through an oestrogen receptor (ER) alpha-dependent pathway. Furthermore, while treatment with ERb antagonist was inefficient, ERa antagonist (MPP) and tamoxifen decreased lung tumour volumes, altered blood and lymphatic vasculature and reduced VEGFA and bFGF levels in females, but not in males. Finally, the quantification of lymphatic and blood vasculature of lung adenocarcinoma biopsies from patients aged between 35 and 55 years revealed more extensive lymphangiogenesis and angiogenesis in tumour samples issued from women than from men. In conclusion, our findings highlight an E2/ERa-dependent modulation of lymphatic and blood vascular components of lung tumour microenvironment. Our study has potential clinical implication in a personalised medicine perspective by pointing to the importance of oestrogen status or supplementation on lung cancer development that should be considered to adapt therapeutic strategies.
Disciplines :
Oncology
Author, co-author :
Dubois, Charline; Université de Liège - ULiège > Sciences biomédicales et précliniques > Laboratoire de biologie des tumeurs et du développement
Rocks, Natacha ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de biologie des tumeurs et du développement
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Primac, Irina ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Gallez, Anne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des Tumeurs et du développement
Garcia-Caballero, Melissa
Gérard, Céline; Université de Liège - ULiège > Sciences biomédicales et précliniques > Laboratoire de Biologie des Tumeurs et du Développement
Brouchet, Laurent; Thoracic Surgery Department, University Hospital CHU Toulouse, Toulouse, France
Noël, Agnès ; Université de Liège - ULiège > Sciences biomédicales et précliniques > Laboratoire de biologie des tumeurs et du développement
Lenfant, Françoise; INSERM UMR1048, Institut des Maladies Métaboliques et Cardiovasculaires – I2MC, University of Toulouse III Paul Sabatier, UPS, Toulouse, France
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de biologie des tumeurs et du développement
Pequeux, Christel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Lymph/angiogenesis contributes to sex differences in lung cancer through oestrogen receptor alpha signalling
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