Babula Aneta, Gałuszka-Bulaga Adrianna, Węglarczyk Kazimierz, Siedlar Maciej, Baj-Krzyworzeka Monika
Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Kraków, Poland.
Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-530 Kraków, Poland.
Oncol Lett. 2023 Aug 7;26(3):413. doi: 10.3892/ol.2023.13999. eCollection 2023 Sep.
During tumor progression, monocytes circulating in the blood or infiltrating tissue may be exposed to tumor-derived extracellular vesicles (TEVs). The first stage of such interactions involves binding of TEVs to the surface of monocytes, followed by their internalization. The present study examines the role of CD44 molecules in the interactions between monocytes and EVs derived from colon cancer cell lines (HCT116 and SW1116). The efficiency of the attachment and engulfment of TEVs by monocytes is linked to the number of TEVs and time of exposure/interaction. The two investigated TEVs, TEVs and TEVs, originating from HCT116 and SW1116 cells, respectively, differ in hyaluronan (HA) cargo, which reflects HA secretion by parental cancer cells. HA-rich TEVs are internalized more effectively in comparison with HA-low TEVs. Blocking of CD44 molecules on monocytes by anti-CD44 monoclonal antibody significantly decreased the engulfment of TEVs but not that of TEVs after 30 min contact, suggesting the involvement of the HA-CD44 axis. The three subsets of monocytes, classical, intermediate and non-classical, characterized by gradual changes in the expression of CD14 and CD16 markers, also differ in the expression of CD44. The highest expression of CD44 molecules was observed in the intermediate monocyte subset. Blocking of CD44 molecules decreased the internalization of HA-rich TEVs in all three subsets, which is associated with CD44 expression level. It was hypothesized that HA carried by TEVs, potentially as a component of the 'corona' coating, may facilitate the interaction between subsets of monocytes and TEVs, which may influence the fate of TEVs (such as the rate of TEVs adhesion and engulfment) and change monocyte activity.
在肿瘤进展过程中，循环于血液中或浸润组织的单核细胞可能会接触到肿瘤衍生的细胞外囊泡（TEV）。此类相互作用的第一阶段涉及TEV与单核细胞表面的结合，随后被单核细胞内化。本研究探讨了CD44分子在单核细胞与源自结肠癌细胞系（HCT116和SW1116）的细胞外囊泡（EV）相互作用中的作用。单核细胞对TEV的附着和吞噬效率与TEV的数量以及暴露/相互作用时间有关。分别源自HCT116和SW1116细胞的两种被研究的TEV，即TEV和TEV，在透明质酸（HA）含量上有所不同，这反映了亲代癌细胞的HA分泌情况。与HA含量低的TEV相比，富含HA的TEV更有效地被内化。用抗CD44单克隆抗体阻断单核细胞上的CD44分子，在接触30分钟后，显著降低了TEV的吞噬，但未降低TEV的吞噬，这表明HA - CD44轴参与其中。以CD14和CD16标志物表达逐渐变化为特征的单核细胞的三个亚群，在CD44表达上也存在差异。在中间单核细胞亚群中观察到CD44分子的最高表达。阻断CD44分子降低了所有三个亚群中富含HA的TEV的内化，这与CD44表达水平相关。据推测，TEV携带的HA可能作为“冠状”涂层的一个成分，促进单核细胞亚群与TEV之间的相互作用，这可能影响TEV的命运（如TEV的黏附和吞噬速率）并改变单核细胞的活性。
