Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

Journal Article · Sun Apr 15 04:00:00 EDT 2012 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2012.01.024· OSTI ID:22212323

Yanagawa, Takashi ^[1]; Shinozaki, Tetsuya ^[1]; Watanabe, Hideomi ^[2]; Saito, Kenichi ^[1]; Raz, Avraham ^[3]; Takagishi, Kenji ^[1]

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1. Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan)
2. Department of Physical Therapy, Gunma University School of Health Science, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan)
3. Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, 110 E. Warren Ave., Detroit, MI (United States)

Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

• OSTI ID: 22212323
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 7 Vol. 318; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CATTLE
CHEMOTHERAPY
FIBROBLASTS
FIBROSARCOMAS
GROWTH FACTORS
LYMPH NODES
METASTASES
PEROXIDASES
RADIOTHERAPY
RECEPTORS