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: Kayoko Takahashi, Yasushi Saga, Hiroaki Mizukami, Yuji Takei, Masashi Urabe, Akihiro Kume, Mitsuaki Suzuki, Keiya Ozawa
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 12 Pg. 2272-7 (Dec 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21910784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• VEGFC protein, human
• Vascular Endothelial Growth Factor C

Topics

• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Endometrial Neoplasms (pathology)
• Female
• Humans
• Lymph Nodes (metabolism, pathology)
• Lymphangiogenesis
• Lymphatic Metastasis (pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Vascular Endothelial Growth Factor C (biosynthesis, genetics, metabolism)