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

Abstract

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 betweenmore » 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.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [1]
  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)
Publication Date:
OSTI Identifier:
22212323
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 318; Journal Issue: 7; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CATTLE; CHEMOTHERAPY; FIBROBLASTS; FIBROSARCOMAS; GROWTH FACTORS; LYMPH NODES; METASTASES; PEROXIDASES; RADIOTHERAPY; RECEPTORS

Citation Formats

Yanagawa, Takashi, Shinozaki, Tetsuya, Watanabe, Hideomi, Saito, Kenichi, Raz, Avraham, and Takagishi, Kenji. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas. United States: N. p., 2012. Web. doi:10.1016/J.YEXCR.2012.01.024.
Yanagawa, Takashi, Shinozaki, Tetsuya, Watanabe, Hideomi, Saito, Kenichi, Raz, Avraham, & Takagishi, Kenji. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas. United States. https://doi.org/10.1016/J.YEXCR.2012.01.024
Yanagawa, Takashi, Shinozaki, Tetsuya, Watanabe, Hideomi, Saito, Kenichi, Raz, Avraham, and Takagishi, Kenji. 2012. "Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas". United States. https://doi.org/10.1016/J.YEXCR.2012.01.024.
@article{osti_22212323,
title = {Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas},
author = {Yanagawa, Takashi and Shinozaki, Tetsuya and Watanabe, Hideomi and Saito, Kenichi and Raz, Avraham and Takagishi, Kenji},
abstractNote = {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.},
doi = {10.1016/J.YEXCR.2012.01.024},
url = {https://www.osti.gov/biblio/22212323}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 7,
volume = 318,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 2012},
month = {Sun Apr 15 00:00:00 EDT 2012}
}