Lymph/angiogenesis contributes to sex differences in lung cancer through oestrogen receptor alpha signalling

Autor: Céline Gérard, Charline Dubois, Silvia Blacher, Agnès Noël, Natacha Rocks, Françoise Lenfant, Didier Cataldo, Anne Gallez, Irina Primac, Laurent Brouchet, Melissa García-Caballero, Christel Pequeux
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Cancer Research
Angiogenesis
Endocrinology
Diabetes and Metabolism
Cell Culture Techniques
angiogenesis
Carcinoma
Lewis Lung
Mice
0302 clinical medicine
Endocrinology
gender
Sex Characteristics
tamoxifen
Sciences bio-médicales et agricoles
Middle Aged
respiratory system
Estrogen Receptor alpha -- physiology
oestrogen receptor
Lymphangiogenesis
lymphangiogenesis
medicine.anatomical_structure
Lymphatic system
Oncology
030220 oncology & carcinogenesis
Adenocarcinoma
Female
Lymph
Signal Transduction
medicine.drug
Adult
Carcinoma
Lewis Lung -- epidemiology
Transfection
03 medical and health sciences
medicine
sex
Animals
Humans
Lung cancer
Cell Proliferation
Lung
business.industry
Estrogen Receptor alpha
medicine.disease
microenvironment
lung cancer
030104 developmental biology
Cancer research
business
Tamoxifen
Zdroj: Endocrine-related cancer, 26 (2
ISSN: 1479-6821
1351-0088
DOI: 10.1530/erc-18-0328
Popis: 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.
info:eu-repo/semantics/published
Databáze: OpenAIRE
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