title: Development of a mouse model for lymph node metastasis with endometrial cancer.
abstract: Controlling lymph node metastasis is currently a key issue in cancer therapy. Lymph node metastasis is one of the most important prognostic factors in various types of cancers, including endometrial cancer. Vascular endothelial growth factor-C (VEGF-C) plays a crucial role in lymphangiogenesis, and is implicated to play an important role in lymph node metastasis. To evaluate the role of VEGF-C in lymph node metastasis, we developed an animal model by using an endometrial cancer cell line, HEC1A. This cell line is not invasive by nature and secretes moderate amounts of VEGF-C; intrauterine injection of HEC1A cells into Balb/c nude mice resulted in uterine cancer with lymph node metastasis after 8 weeks. To analyze the contribution of VEGF-C to lymph node metastasis, its corresponding gene was stably introduced into HEC1A cells (HEC1A/VEGF-C), which then produced more than 10 times the amount of VEGF-C. The number of lymph node metastases was significantly higher in HEC1A/VEGF-C cells than in HEC1A cells (3.2 vs 1.1 nodes/animal, respectively). Augmented lymphangiogenesis was observed within tumors when HEC1A/VEGF-C cells were inoculated. These results indicate that VEGF-C plays a critical role in lymph node metastasis, in addition to serving as a platform to test the efficacy of various therapeutic modalities against lymph node metastasis.
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, Tochigi, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Masashi
authors.initials: M
authors.lastname: Urabe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kume
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C