升高的 SPINK1 水平在血管生成和 ALL 细胞的跨内皮迁移中起作用。

Raised SPINK1 levels play a role in angiogenesis and the transendothelial migration of ALL cells.

机构信息

Medical Laboratory, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan City, Guangdong Province, China.

Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, Guangdong, China.

出版信息

Sci Rep. 2022 Feb 22;12(1):2999. doi: 10.1038/s41598-022-06946-6.

DOI:10.1038/s41598-022-06946-6

PMID:35194087

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8864021/

Abstract

The present study was designed to assess whether raised Serine protease inhibitor Kazal type 1 (SPINK1) expressions modulates angiogenesis. Human umbilical vein endothelial cells (HUVECs) exposed to SPINK1 were noted to exhibit raised expressions of interleukin-8 (IL-8) as well as VCAM-1 and ICAM-1 cell adhesion molecules in a dose-dependent manner. In co-culture system of HUVECs and Acute lymphoblastic leukemia (ALL) cells, SPINK1 exposure also resulted in enhanced endothelial cell motility and ALL cells trans-endothelial migration. High concentrations of SPINK1 caused in vitro cellular reorganization into tubes in Matrigel-cultured HUVECs and induced in vivo vascularization and brain infiltration of NOD/SCID ALL model mice. The further transcriptomic analysis indicated that SPINK1 treatment altered several biological processes of endothelial cells and led to activation of the MAPK pathway. This study is the first to determine the neovascularization effects of raised SPINK1.

摘要

本研究旨在评估丝氨酸蛋白酶抑制剂 Kazal 型 1（SPINK1）的升高表达是否调节血管生成。研究发现，SPINK1 暴露的人脐静脉内皮细胞（HUVEC）以剂量依赖性方式表现出白细胞介素-8（IL-8）以及 VCAM-1 和 ICAM-1 细胞黏附分子的升高表达。在 HUVEC 和急性淋巴细胞白血病（ALL）细胞的共培养系统中，SPINK1 暴露也导致内皮细胞迁移和 ALL 细胞跨内皮迁移增强。高浓度的 SPINK1 导致 Matrigel 培养的 HUVEC 中细胞体外重组形成管，并诱导 NOD/SCID ALL 模型小鼠体内血管生成和脑浸润。进一步的转录组分析表明，SPINK1 处理改变了内皮细胞的几个生物学过程，并导致 MAPK 途径的激活。这项研究首次确定了升高的 SPINK1 的血管新生作用。