title: Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model.
abstract: In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor dissemination, characterized by the presence of melanoma cells between the primary lesion and the draining regional lymph node basin that is clinically associated with poor prognosis. In this study, we aimed to establish an experimental animal model of melanoma ITM, as research progress in this field has been hampered by a lack of suitable experimental models. We reproduced melanoma ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a mouse with lymphedema (LE). The tumor cells at the ITM site were highly proliferative, and mice with ITMs were more likely than control mice to develop distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor-associated blood vessels were increased in the primary tumor site of the LE mice. Our established ITM melanoma mouse model enabled us to clarify the molecular determinants and pathophysiology of ITM. This ITM model is also comparable to the unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined the importance of lymphangiogenic factors in the tumor dissemination through the lymphatic system.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido at Sapporo (UHS), Sapporo, Japan. ko03252000@yahoo.co.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Oashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Oyama
authors.forename: Emi
authors.initials: E
authors.lastname: Funayama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019394:Ki-67 Antigen / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000503:physiopathology / Q000556:secondary*; D008207:Lymphatic Metastasis / Q000473:pathology; D042601:Lymphatic Vessels / Q000473:pathology / Q000502:physiology; D008209:Lymphedema / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008546:Melanoma, Experimental / Q000503:physiopathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011379:Prognosis; D012878:Skin Neoplasms / Q000473:pathology* / Q000503:physiopathology
chemical_list: D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D008156:Luciferases