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VEGF-C improves regeneration and lymphatic reconnection of transplanted autologous lymph node fragments: An animal model for secondary lymphedema treatment.

ABSTRACT: Secondary lymphedema occurs after for example breast cancer surgery and radiation in 20-50% of the patients. Due to the poor outcomes of surgical treatments in the past, the therapy often remains symptomatic. However, avascular transplantation of autologous lymph node fragments (LN-Tx) combined with postoperative injections of vascular endothelial growth factor-C (VEGF-C) emerges as a potential surgical therapy. In this study, adult rats underwent LN-Tx to investigate the following parameters of VEGF-C application: time point, location and dosage. Furthermore, the influences of VEGF-C on lymphatic reconnection and transplant regeneration were analyzed. The reconnection was investigated using intradermally injected blue dye and the regeneration was evaluated histologically using hematoxylin-eosin (H&E) staining and immunohistochemistry. The higher dosage enhanced the reconnection rates significantly and showed a statistical tendency of improving regeneration. An application on early postoperative days and the injection into the medial thigh improved the reconnection significantly. However, these variables did not affect the regeneration statistically. This study confirms that LN-Tx combined with lymphatic growth factor VEGF-C is a possible approach in the therapy of secondary lymphedema and shows the important role of VEGF-C application parameters.

SUBMITTER: Schindewolffs L

PROVIDER: S-EPMC4257760 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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VEGF-C improves regeneration and lymphatic reconnection of transplanted autologous lymph node fragments: An animal model for secondary lymphedema treatment.

Schindewolffs Lia L Breves Gerhard G Buettner Manuela M Hadamitzky Catarina C Pabst Reinhard R

Immunity, inflammation and disease 20141117 3

Secondary lymphedema occurs after for example breast cancer surgery and radiation in 20-50% of the patients. Due to the poor outcomes of surgical treatments in the past, the therapy often remains symptomatic. However, avascular transplantation of autologous lymph node fragments (LN-Tx) combined with postoperative injections of vascular endothelial growth factor-C (VEGF-C) emerges as a potential surgical therapy. In this study, adult rats underwent LN-Tx to investigate the following parameters of ...[more]

PMID: 25505549

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Project description:BackgroundSentinel lymph node metastasis is a common and early event in the metastatic process of head and neck squamous cell carcinoma (HNSCC) and is the most powerful prognostic factor for survival of HNSCC patients. 3-O-acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from seeds of Vigna sinensis K., has been reported to have potent anti-angiogenesis and anti-tumor activities. However, its effects on tumor-related lymphangiogenesis and lymph node metastasis are not yet understood.MethodsThe in vitro inhibitory effects of 3AOA on VEGF-A-induced lymphangiogenesis were investigated via in vitro experiments using mouse oral squamous cell carcinoma (SCCVII) cells and human lymphatic microvascular endothelial cells (HLMECs). The in vivo inhibitory effects of 3AOA on VEGF-A-induced lymphangiogenesis and sentinel lymph node metastasis were investigated in an oral cancer sentinel lymph node (OCSLN) animal model.Results3AOA inhibited tumor-induced lymphangiogenesis and sentinel lymph node metastasis in an OCSLN animal model, and reduced expression of VEGF-A, a lymphangiogenic factor in hypoxia mimetic agent CoCl2-treated SCCVII cells. 3AOA inhibited proliferation, tube formation, and migration of VEGF-A-treated HLMECs. The lymphatic vessel formation that was stimulated in vivo in a by VEGF-A Matrigel plug was reduced by 3AOA. 3AOA suppressed phosphorylation of vascular endothelial growth factor (VEGFR) -1 and - 2 receptors that was stimulated by VEGF-A. In addition, 3AOA suppressed phosphorylation of the lymphangiogenesis-related downstream signaling factors PI3K, FAK, AKT, and ERK1/2. 3AOA inhibited tumor growth, tumor-induced lymphangiogenesis, and sentinel lymph node metastasis in a VEGF-A-induced OCSLN animal model that was established using VEGF-A overexpressing SCCVII cells.Conclusion3AOA inhibits VEGF-A-induced lymphangiogenesis and sentinel lymph node metastasis both in vitro and in vivo. The anti-lymphangiogenic effects of 3AOA are probably mediated via suppression of VEGF-A/VEGFR-1 and VEGFR-2 signaling in HLMECs, and can be a useful anti-tumor agent to restrict the metastatic spread of oral cancer.

Dataset Information

VEGF-C improves regeneration and lymphatic reconnection of transplanted autologous lymph node fragments: An animal model for secondary lymphedema treatment.

Publications

VEGF-C improves regeneration and lymphatic reconnection of transplanted autologous lymph node fragments: An animal model for secondary lymphedema treatment.

Similar Datasets

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