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International Journal of Breast Cancer
Volume 2011 (2011), Article ID 867152, 10 pages
http://dx.doi.org/10.4061/2011/867152
Research Article

Lymphangiogenesis and Axillary Lymph Node Metastases Correlated with VEGF-C Expression in Two Immunocompetent Mouse Mammary Carcinoma Models

1Division of Life Sciences, Department of Anatomy and Cell Biology, Osaka Medical College, 2-7 Daigaku-Machi, Takatsuki, Osaka 569-8686, Japan
2Laboratory of Anatomy and Histopathology, Faculty of Health Science, Osaka Health Science University, 1-9-27 Temma, Kita-ku, Osaka 530-0043, Japan
3Laboratory Animal Center, Osaka Medical College, 2-7 Daigaku-Machi, Takatsuki, Osaka 569-8686, Japan

Received 15 June 2011; Accepted 17 August 2011

Academic Editor: Luciane R. Cavalli

Copyright © 2011 Yuko Ito et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Lymphangiogenesis and the expression of vascular endothelial cell growth factor C (VEGF-C) in tumors have been considered to be causally promoting lymphatic metastasis. There are only a few studies on lymphatic metastasis in immunocompetent allograft mouse models. To study the relationship between VEGF-C-mediated lymphangiogenesis and axillary lymph node metastasis, we used two mouse mammary carcinoma cell lines; the BJMC338 has a low metastatic propensity, whereas the BJMC3879 has a high metastatic propensity although it originated from the former cell line. Each cell line was injected separately into two groups of female BALB/c mice creating in vivo mammary cancer models. The expression level of VEGF-C in BJMC3879 was higher than BJMC338. As the parent cell line, BJMC3879-derived tumors showed higher expression of VEGF-C compared to BJMC338-derived tumors. This higher expression of VEGF-C in BJMC3879-derived tumors was associated with marked increase in infiltrating macrophages and enhanced expression of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) reflecting increased tumoral lymphatic density and subsequent induction of axillary lymph node metastasis. Our mouse mammary carcinoma models are allotransplanted tumors showing the same axillary lymph node metastatic spectrum as human breast cancers. Therefore, our mouse models are ideal for exploring the various molecular mechanisms of cancer metastasis.