PURPOSE: Unlike carcinomas, soft-tissue sarcoma (STS) rarely exhibit lymphatic spread. Consequently, we examined expression and function of vascular endothelial growth factor (VEGF)-C and STS-associated lymphatic vessel density (LVD) components of this process. EXPERIMENTAL DESIGN: VEGF-C and VEGF-A mRNA and VEGF-C protein expression were evaluated in STS, STS cell lines, and breast cancers (reverse transcription-PCR, quantitative reverse transcription-PCR, and ELISA). STS cell conditioned medium after VEGF-C knockdown was examined for endothelial cell proliferation and migration effects (MTS and migration assays). Paraffin-embedded human lymph node-negative and lymph node-positive STS and lymph node-negative and lymph node-positive breast cancers were examined for VEGF-C, D2-40, and CD31 expression (immunohistochemistry). LVD differences were analyzed by Wilcoxon rank-sum tests. RESULTS: STS and breast cancer VEGF-C expression was comparable and higher than normal tissue levels. STS cells secreted functional VEGF-C: STS conditioned medium induced lymphatic endothelial cell proliferation and migration, which was abrogated by STS cell VEGF-C knockdown. STS and breast cancer intratumoral LVD was similar. STS peritumoral LVD (PT-LVD) was reduced versus breast cancer PT-LVD (P < 0.001). Significantly higher PT-LVD was observed in lymph node-positive versus lymph node-negative STS; lymphatic spreading STS subtypes also had higher LVD. STS VEGF-C expression and PT-LVD lacked correlation, and many lymph node-negative STS had high PT-LVD, suggesting complexity in this metastatic process. CONCLUSIONS: Compared with breast cancers, STS exhibited lower PT-LVD independent of VEGF-C expression, which may underlie STS lymph node metastasis rarity. Moreover, lymphatic vessels appear necessary but not sufficient to sustain STS lymphatic spread. Examining STS "nonlymphatic" dissemination may help elucidate mechanisms of lymphatic spread, insights critically important to cancer metastasis control.
PURPOSE: Unlike carcinomas, soft-tissue sarcoma (STS) rarely exhibit lymphatic spread. Consequently, we examined expression and function of vascular endothelial growth factor (VEGF)-C and STS-associated lymphatic vessel density (LVD) components of this process. EXPERIMENTAL DESIGN:VEGF-C and VEGF-A mRNA and VEGF-C protein expression were evaluated in STS, STS cell lines, and breast cancers (reverse transcription-PCR, quantitative reverse transcription-PCR, and ELISA). STS cell conditioned medium after VEGF-C knockdown was examined for endothelial cell proliferation and migration effects (MTS and migration assays). Paraffin-embedded human lymph node-negative and lymph node-positive STS and lymph node-negative and lymph node-positive breast cancers were examined for VEGF-C, D2-40, and CD31 expression (immunohistochemistry). LVD differences were analyzed by Wilcoxon rank-sum tests. RESULTS: STS and breast cancerVEGF-C expression was comparable and higher than normal tissue levels. STS cells secreted functional VEGF-C: STS conditioned medium induced lymphatic endothelial cell proliferation and migration, which was abrogated by STS cell VEGF-C knockdown. STS and breast cancer intratumoral LVD was similar. STS peritumoral LVD (PT-LVD) was reduced versus breast cancer PT-LVD (P < 0.001). Significantly higher PT-LVD was observed in lymph node-positive versus lymph node-negative STS; lymphatic spreading STS subtypes also had higher LVD. STS VEGF-C expression and PT-LVD lacked correlation, and many lymph node-negative STS had high PT-LVD, suggesting complexity in this metastatic process. CONCLUSIONS: Compared with breast cancers, STS exhibited lower PT-LVD independent of VEGF-C expression, which may underlie STS lymph node metastasis rarity. Moreover, lymphatic vessels appear necessary but not sufficient to sustain STS lymphatic spread. Examining STS "nonlymphatic" dissemination may help elucidate mechanisms of lymphatic spread, insights critically important to cancer metastasis control.
Authors: Keila E Torres; Quan-Sheng Zhu; Katelynn Bill; Gonzalo Lopez; Markus P Ghadimi; Xianbiao Xie; Eric D Young; Juehui Liu; Theresa Nguyen; Svetlana Bolshakov; Roman Belousov; Suizhau Wang; Guy Lahat; Jun Liu; Belinda Hernandez; Alexander J Lazar; Dina Lev Journal: Clin Cancer Res Date: 2011-05-03 Impact factor: 12.531
Authors: Colleen L Doçi; Constantinos M Mikelis; Michail S Lionakis; Alfredo A Molinolo; J Silvio Gutkind Journal: Cancer Res Date: 2015-05-07 Impact factor: 12.701
Authors: Guy Lahat; Quan-Sheng Zhu; Kai-Lieh Huang; Suizhao Wang; Svetlana Bolshakov; Jeffery Liu; Keila Torres; Robert R Langley; Alexander J Lazar; Mien Chie Hung; Dina Lev Journal: PLoS One Date: 2010-04-16 Impact factor: 3.240
Authors: Sharon M Landers; Angela D Bhalla; XiaoYan Ma; Kristelle Lusby; Davis Ingram; Ghadah Al Sannaa; Wei-Lien Wang; Alexander J Lazar; Keila E Torres Journal: J Cancer Sci Clin Ther Date: 2020-10-27