title: Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis.
abstract: The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation.
authors: Université Pierre et Marie Curie, University Paris 06, Paris, France.
authors: Kiarash
authors: K
authors: Khosrotehrani
authors: Sau
authors: S
authors: Nguyen Huu
authors: Aurélie
authors: A
authors: Prignon
authors: Marie-Françoise
authors: MF
authors: Avril
authors: Françoise
authors: F
authors: Boitier
authors: Michèle
authors: M
authors: Oster
authors: Laurent
authors: L
authors: Mortier
authors: Marie-Aleth
authors: MA
authors: Richard
authors: Eve
authors: E
authors: Maubec
authors: Delphine
authors: D
authors: Kerob
authors: Sandrine
authors: S
authors: Mansard
authors: Charbel
authors: C
authors: Merheb
authors: Philippe
authors: P
authors: Moguelet
authors: Dany
authors: D
authors: Nassar
authors: Sarah
authors: S
authors: Guégan
authors: Selim
authors: S
authors: Aractingi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D007249:Inflammation; D042583:Lymphangiogenesis; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000473:pathology*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic; D011270:Pregnancy, Animal; D012867:Skin / Q000473:pathology
chemical_list: D019788:Fluorodeoxyglucose F18