Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 of the Centre National de la Recherche Scientifique, University of Lille, Villeneuve d'Ascq, F-59655 Lille, France.
Molecules. 2018 Oct 22;23(10):2718. doi: 10.3390/molecules23102718.
Heparan sulfate 3--sulfotransferases (HS3STs) catalyze the maturation step of heparan sulfate (HS) 3--sulfation. This modification is relatively rare. Moreover, only a few biological processes have been described to be influenced by 3--sulfated HS, and few ligands have been identified so far. Among them, neuropilin-1 (Nrp1) was reported to exhibit tumor-promoting properties by enhancing the action of various growth factors. We recently demonstrated that transient overexpression of HS3ST2, 3B or 4 enhanced the proliferation of breast cancer MDA-MB-231 cells and promote efficient protection against pro-apoptotic stimuli. Hence, we hypothesized that the pro-tumoral activity of these HS3STs could depend on the expression of Nrp1. To test this, MDA-MB-231 cells were stably transfected with a construct encoding HS3ST3B and the expression of Nrp1 was down-regulated by RNA interference. First, we confirmed that stable expression of HS3ST3B effectively increased cell proliferation and viability. Silencing the expression of Nrp1 markedly attenuated the promoting effects of HS3ST3B, while the same treatment had only a moderate effect on the behavior of the parental cells. Altogether, our findings support the idea that the tumor-promoting effects of HS3ST3B could be dependent on the expression of Nrp1 in cancer cells.
硫酸乙酰肝素 3-硫酸转移酶（HS3STs）催化硫酸乙酰肝素（HS）3-硫酸化的成熟步骤。这种修饰相对较少。此外，只有少数生物学过程被描述为受 3-硫酸化 HS 影响，到目前为止，很少有配体被鉴定出来。其中，神经纤毛蛋白-1（Nrp1）被报道通过增强各种生长因子的作用具有促进肿瘤的特性。我们最近证明，HS3ST2、3B 或 4 的瞬时过表达增强了乳腺癌 MDA-MB-231 细胞的增殖，并有效地促进了对促凋亡刺激的保护。因此，我们假设这些 HS3STs 的促肿瘤活性可能取决于 Nrp1 的表达。为了验证这一点，MDA-MB-231 细胞被稳定转染了编码 HS3ST3B 的构建体，并用 RNA 干扰下调 Nrp1 的表达。首先，我们证实 HS3ST3B 的稳定表达有效地增加了细胞增殖和活力。沉默 Nrp1 的表达显著减弱了 HS3ST3B 的促进作用，而相同的处理对亲本细胞的行为只有适度的影响。总之，我们的研究结果支持了这样一种观点，即 HS3ST3B 的促肿瘤作用可能依赖于癌细胞中 Nrp1 的表达。
