Molecular profile and proliferative responses of rat lymphatic endothelial cells in culture.
Molecular profile and proliferative responses of rat lymphatic endothelial cells in culture.
复制标题
培养物中大鼠淋巴内皮细胞的分子谱和增殖反应。
DOI：
10.1089/lrb.2006.4.119
复制
发表时间：
2006
影响因子：
1.4
通讯作者：
Ran,Sophia
中科院分区：
文献类型：
--
作者：
Whitehurst,Brandt;Eversgerd,Chad;Flister,Michael;Bivens,ChristopherM;Pickett,Brent;Zawieja,DavidC;Ran,Sophia
背景：淋巴管生成在许多实体瘤的转移中起重要作用。为了在受控条件下研究淋巴管生成，需要一种体外模型。这项工作的目标是建立这样的anin vitromodel，通过确定大鼠肠系膜淋巴管内皮细胞（RMLEC）的分子概况，并表征其增殖反应的血管生成和淋巴管生成因子，如血管内皮生长因子A和C（VEGF-A和VEGF-C）。方法和结果：RMLEC强烈表达大多数血管特异性标志物，包括Prox-1，LYVE-1，和VEGFR-3。RMLEC的增殖具有血清和肝素依赖性。在低浓度（2%）血清中，外源性VEGF-A和VEGFC刺激RMLEC以线性和剂量依赖性的方式。这种作用被抗VEGF-A和VEGF-C抗体以及可溶性Tie-2和Flt-4融合蛋白消除。结论：培养的RMLEC保留了与体内淋巴管内皮细胞表型一致的分子特征，并对VEGF-A或VEGF-C因子产生应答。VEGFA能够挽救由中和VEGF-C抗体或可溶性Tie-2融合蛋白抑制的RMLEC增殖。这些结果支持血管生成因子和淋巴管生成因子之间存在串扰。这项工作建立了实验条件，允许淋巴管内皮细胞对淋巴管生成调节剂的反应的体外模型。使用该模型的初步结果表明，VEGF-A，VEGF-C和血管生成素协同工作，以促进体内淋巴管生成。
Background: Lymphangiogenesis plays an important role in metastasis of many solid tumors. To study lymphangiogenesis under controlled conditions, anin vitromodel is needed. The goal of this work was to establish such anin vitromodel by determining a molecular profile of rat mesenteric lymphatic endothelial cells (RMLEC) and characterizing their proliferative responses to angiogenic and lymphangiogenic factors, such as vascular endothelial growth factor A and C (VEGF-A and VEGF-C).Methods and Results: RMLEC strongly expressed most lymphatic-specific markers, including Prox-1, LYVE-1, and VEGFR-3. Proliferation of RMLEC was serum and heparin dependent. In the presence of low (2%) serum concentration, exogenously added VEGF-A and VEGFC stimulated RMLEC in a linear and dose-dependent manner. This effect was abrogated by anti-VEGF-A and VEGF-C antibodies, as well as by soluble Tie-2 and Flt-4 fusion proteins. Abrogation was reversed by VEGF-A, suggesting that this factor as an important regulator of lymphangiogenesis.Conclusions: Cultured RMLEC preserved a molecular profile consistent with the phenotype of lymphatic endotheliumin vivoand respond to either VEGF-A or VEGF-C factors. VEGFA was able to rescue RMLEC proliferation inhibited by a neutralizing VEGF-C antibody or soluble Tie-2 fusion protein. These results support the existence of cross-talk among angiogenic and lymphangiogenic factors. This work established experimental conditions that allowin vitromodeling of lymphatic endothelial responses to lymphangiogenic regulators. Preliminary results using this model suggest that VEGF-A, VEGF-C, and angiopoietins work in concert to promote lymphangiogenesisin vivo.