A Comparative Study of Adhesion of Melanoma and Breast Cancer Cells to Blood and Lymphatic Endothelium
A Comparative Study of Adhesion of Melanoma and Breast Cancer Cells to Blood and Lymphatic Endothelium
复制标题
DOI：
10.1089/lrb.2012.0007
复制
发表时间：
2012-01-01
影响因子：
1.4
通讯作者：
Martin, Stewart G.
中科院分区：
文献类型：
--
作者：
Safuan, Sabreena;Storr, Sarah J.;Martin, Stewart G.
背景：淋巴血管侵袭（LVI）是转移级联反应中的重要一步；肿瘤细胞迁移并粘附到血液和淋巴管上，随后侵入血管壁并随后发生全身性扩散。尽管原发性乳腺癌和黑色素瘤具有丰富的血管网络，但 LVI 本质上主要是淋巴管。虽然肿瘤细胞与血液内皮的粘附已被广泛研究，但关于肿瘤细胞与淋巴管内皮细胞粘附的信息很少。 方法和结果：乳腺癌（MDA-MB-231和MCF7）和黑色素瘤（MeWo和SKMEL-30）细胞与淋巴管（hTERT-LEC和HMVEC dLy Neo）和血液（HUVEC和hMEC-1）内皮细胞的粘附使用静态粘附测定进行评估。还检查了炎症条件、肿瘤坏死因子-α (TNF-α) 刺激内皮细胞和肿瘤细胞对粘附过程的影响。此外，使用单轴（划痕）测定研究了 TNF-α 刺激对肿瘤细胞迁移的影响。与淋巴管内皮细胞相比，乳腺癌和黑色素瘤细胞对血液的粘附水平更高（p < 0.001）。 TNF-α刺激内皮细胞或单独刺激肿瘤细胞，不会显着改变肿瘤-内皮细胞粘附或模式。当用 TNF-α 刺激肿瘤和内皮细胞时，观察到粘附力显着增加 (p < 0.01)，在淋巴细胞模型中明显更高 (p < 0.001)。所有肿瘤细胞系的 TNF-α 刺激均显着增加其迁移率 (p < 0.01)。 结论：结果表明，淋巴管-肿瘤细胞粘附引起的转移可能受到细胞因子刺激的调节，这可能是乳腺癌和黑色素瘤的重要治疗靶点。
Background: Lymphovascular invasion (LVI) is an important step in the metastatic cascade; tumor cell migration and adhesion to blood and lymphatic vessels is followed by invasion through the vessel wall and subsequent systemic spread. Although primary breast cancers and melanomas have rich blood vascular networks, LVI is predominately lymphatic in nature. Whilst the adhesion of tumor cells to blood endothelium has been extensively investigated, there is a paucity of information on tumor cell adhesion to lymphatic endothelium.Methods and Results: Breast cancer (MDA-MB-231 and MCF7) and melanoma (MeWo and SKMEL-30) cell adhesion to lymphatic (hTERT-LEC and HMVEC dLy Neo) and blood (HUVEC and hMEC-1) endothelial cells were assessed using static adhesion assays. The effect of inflammatory conditions, tumor necrosis factor-alpha (TNF-alpha) stimulation of endothelial and tumor cells, on the adhesive process was also examined. In addition, the effects of TNF-alpha stimulation on tumor cell migration was investigated using haplotaxis (scratch wound) assays. Breast cancer and melanoma cells exhibited higher levels of adhesion to blood compared to lymphatic endothelial cells (p < 0.001). TNF-alpha stimulation of endothelial cells, or of tumor cells alone, did not significantly alter tumor-endothelial cell adhesion or patterns. When both tumor and endothelial cells were stimulated with TNF-alpha, a significant increase in adhesion was observed (p < 0.01), which was notably higher in the lymphatic cell models (p < 0.001). TNF-alpha-stimulation of all tumor cell lines significantly increased their migration rate (p < 0.01).Conclusions: Results suggest that metastasis resultant from lymphatic vessel-tumor cell adhesion may be modulated by cytokine stimulation, which could represent an important therapeutic target in breast cancer and melanoma.