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乳腺癌细胞糖基化表型的改变促进了 T3 血清型溶瘤呼肠孤病毒的感染。

Altered Glycan Expression on Breast Cancer Cells Facilitates Infection by T3 Seroptype Oncolytic Reovirus.

机构信息

Louvain Institute of Biomolecular Science and Technology (LIBST), Université Catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.

Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, 15224 Pennsylvania United States.

出版信息

Nano Lett. 2021 Nov 24;21(22):9720-9728. doi: 10.1021/acs.nanolett.1c03608. Epub 2021 Nov 11.

Abstract

Breast cancer is the most common cancer in women. Although current therapies have increased survival rates for some breast cancer types, other aggressive invasive breast cancers remain difficult to treat. As the onset of breast cancer is often associated with the appearance of extracellular markers, these could be used to better target therapeutic agents. Here, we demonstrated by nanobiophysical approaches that overexpression of α-sialylated glycans in breast cancer provides an opportunity to combat cancer cells with oncolytic reoviruses. Notably, a correlation between cellular glycan expression and the mechanical properties of reovirus attachment and infection is observed in a serotype-dependent manner. Furthermore, we enhance the infectivity of reoviruses in malignant cells by the coinjection of α-sialylated glycans. In conclusion, this study supports both the use of reoviruses as an oncolytic agent in nanomedicine and the role of α-sialylated glycans as adjuvants in oncolysis, offering new perspective in oncolytic cancer therapy.

摘要

乳腺癌是女性最常见的癌症。尽管目前的治疗方法已经提高了某些乳腺癌类型的生存率,但其他侵袭性强的乳腺癌仍然难以治疗。由于乳腺癌的发病通常与细胞外标记物的出现有关,因此这些标记物可以更好地用于靶向治疗药物。在这里,我们通过纳米生物物理方法证明,乳腺癌中 α-唾液酸化聚糖的过度表达为用溶瘤性呼肠孤病毒来对抗癌细胞提供了机会。值得注意的是,在依赖于血清型的方式下,观察到细胞糖基表达与呼肠孤病毒附着和感染的机械特性之间存在相关性。此外,我们通过共注射α-唾液酸化聚糖来提高恶性细胞中呼肠孤病毒的感染性。总之,这项研究支持将呼肠孤病毒作为纳米医学中的溶瘤剂以及α-唾液酸化聚糖作为溶瘤作用中的佐剂的用途,为溶瘤癌症治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7310/8631336/9138247c9f7f/nl1c03608_0001.jpg

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