Inhibition of E-selectin expression on the surface of endothelial cells inhibits hepatocellular carcinoma growth by preventing tumor angiogenesis

Autor: Elisabeth Jouve, René Gerolami, Assou El-Battari, Patrick Borentain, Sylvie Carmona, Sylvie Mathieu
Přispěvatelé: Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d’Hépato-Gastro-Entérologie [CHU - APHM] LA CONCEPTION, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_specialty
Carcinoma
Hepatocellular
Lewis X Antigen
[SDV.CAN]Life Sciences [q-bio]/Cancer
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Toxicology
Amiloride
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Vasculogenesis
Antigen
In vivo
Internal medicine
E-selectin
medicine
Animals
Humans
Pharmacology (medical)
Sialyl Lewis X Antigen
ComputingMilieux_MISCELLANEOUS
Cell Proliferation
Pharmacology
Neovascularization
Pathologic
biology
Chemistry
Cell growth
Liver Neoplasms
Endothelial Cells
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Hep G2 Cells
digestive system diseases
In vitro
3. Good health
030104 developmental biology
Endocrinology
Sialyl-Lewis X
Oncology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Cimetidine
E-Selectin
medicine.drug
Zdroj: Cancer Chemotherapy and Pharmacology
Cancer Chemotherapy and Pharmacology, Springer Verlag, 2016, 77 (4), pp.847-856. ⟨10.1007/s00280-016-3006-x⟩
ISSN: 1432-0843
0344-5704
Popis: Interactions between endothelial and tumor cells via E-selectin and sialyl Lewis x (sLex) have been suggested to play a significant role in the development of metastasis and tumor growth. In this work, we tested whether inhibition of E-selectin expression on the surface of endothelial cells might impair endothelial/tumor cells interactions and tumor growth of hepatocarcinoma cells in vitro and in vivo. We used HepG2 cells that highly express sLex antigens and HuH7 cells that do not express sLex. Inhibition of E-selectin expression on the surface of endothelial cells was obtained by using cimetidine and amiloride treatment. Cimetidine and amiloride inhibited, respectively, by 20 and 64 % E-selectin expression by activated endothelial cells and significantly subsequent adhesion of HepG2 cells to activated endothelial cells. Subcutaneous injection of cimetidine or amiloride resulted in a significant inhibition of HepG2 cells tumor growth in nu/nu mice but not of HuH7 cells. Thus, cimetidine and amiloride administration led to an inhibition of 57 and 75 % of HepG2 tumor growth in vivo, respectively. This effect was associated with an inhibition of vasculogenesis as demonstrated by anti-CD31 immunostaining. Inhibition of E-selectin expression allows an anti-tumoral effect on sLex-expressing HCC tumors in vivo. This suggests that interactions between HCC cells and endothelial cells through sLex antigens and E-selectin might be a target for treatment of HCC. Further studies might evaluate the clinical impact of cimetidine and amiloride in the treatment of HCC patients alone or in combination with other anti-tumoral agents.
Databáze: OpenAIRE
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