Open AccessDevelopment of a mouse model for lymph node metastasis with endometrial cancer
Author(s) -
Takahashi Kayoko,
Saga Yasushi,
Mizukami Hiroaki,
Takei Yuji,
Urabe Masashi,
Kume Akihiro,
Suzuki Mitsuaki,
Ozawa Keiya
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02099.x
Subject(s) - lymphangiogenesis , endometrial cancer , metastasis , medicine , lymph , lymph node , cancer research , cancer cell , cancer , lymphatic system , oncology , pathology
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. ( Cancer Sci 2011; 102: 2272–2277)