Zhang L, Zeng M, Fu B M
Department of Biomedical Engineering, The City College of the City University of New York, 160 Convent Ave, New York, NY 10031, USA.
Cell Mol Biol (Noisy-le-grand). 2017 Apr 29;63(4):16-22. doi: 10.14715/cmb/2017.63.4.3.
Sphingosine-1-phosphate (S1P) is a sphingolipid in plasma that plays a critical role in cardiovascular and immune systems. Endothelial surface glycocalyx (ESG) decorating the inner wall of blood vessels is a regulator of multiple vascular functions. To test the hypothesis that S1P can reduce tumor cell adhesion to microvessel walls by protecting the ESG, we quantified the ESG and MDA-MB-231 tumor cell adhesion in the presence and absence of 1μM S1P, and in the presence of the matrix metalloproteinase (MMP) inhibitor in post-capillary venules of rat mesentery. We also measured the microvessel permeability to albumin as an indicator for the microvessel wall integrity. In the absence of S1P, ESG was ~10% of that in the presence of S1P, whereas adherent tumor cells and the permeability to albumin and were ~3.5-fold (after 30 min adhesion) and ~7.7-fold that in the presence of S1P, respectively. In the presence of the MMP inhibitor, the results are similar to those in the presence of S1P. Our results conform to the hypothesis that protecting ESG by S1P inhibits MDA-MB-231 tumor cell adhesion to the microvessel wall.
鞘氨醇-1-磷酸（S1P）是血浆中的一种鞘脂，在心血管和免疫系统中发挥关键作用。覆盖血管内壁的内皮表面糖萼（ESG）是多种血管功能的调节因子。为了验证S1P可通过保护ESG来减少肿瘤细胞与微血管壁黏附的假说，我们在存在和不存在1μM S1P的情况下，以及在大鼠肠系膜毛细血管后微静脉中存在基质金属蛋白酶（MMP）抑制剂的情况下，对ESG和MDA-MB-231肿瘤细胞黏附进行了定量。我们还测量了微血管对白蛋白的通透性，以此作为微血管壁完整性的指标。在不存在S1P的情况下，ESG约为存在S1P时的10%，而黏附的肿瘤细胞以及白蛋白通透性分别约为存在S1P时的3.5倍（黏附30分钟后）和约7.7倍。在存在MMP抑制剂的情况下，结果与存在S1P时相似。我们的结果符合S1P通过保护ESG抑制MDA-MB-231肿瘤细胞与微血管壁黏附的假说。
