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转移性结肠癌细胞来源的外泌体通过增加癌症干细胞标志物 CD133 和 DCLK1 的表达来驱动原发性结肠癌细胞的增殖和迁移。

Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1.

机构信息

Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, kattankulathur, Chengalpattu, Tamil Nadu 603203, India.

Department of Allied Health Sciences. Chettinad Academy of Science and Technology, Kelambakkam, Kanchipuram, Tamil Nadu 603103, India.

出版信息

Tissue Cell. 2023 Oct;84:102163. doi: 10.1016/j.tice.2023.102163. Epub 2023 Jul 13.

Abstract

The exchange of biological material between the neighbouring cells is essential for homeostasis. In pathological conditions, such as cancer, the major challenge in cancer treatment is the abnormal expression of crucial proteins and miRNA exchanged between the cancer cells through extracellular vesicles called exosomes. Clinically, it has been noticed that the primary tumour and the distal metastases are interconnected and co-dependent. The exosomes are key factors responsible for preparing the pre-metastatic niche and communicating between the tumour and the distal metastatic site. Cancer stem cells (CSCs) are a subpopulation of cancer cells with self-renewal characteristics and are shown to be responsible for metastasis. This study aims to understand the effect of metastatic cell line-derived exosomes and their regulation of CSC marker expressions on primary colon cancer cell lines. We have identified that treatment of primary colon cancer cell lines with metastatic colon cancer cell-derived exosomes has significantly increased the proliferation, colony formation, cell migration, and invasion. In addition, there was a significant increase in the number and size of spheroids following the exosomes treatment. We found that this metastatic phenotype is due to the increased expression of CD133 and DCLK1 in primary colon cancer cells.

摘要

相邻细胞之间的生物物质交换对于维持内稳态至关重要。在病理条件下,如癌症,癌症治疗的主要挑战是癌细胞通过称为外泌体的细胞外囊泡异常表达关键蛋白和 miRNA。临床上已经注意到,原发肿瘤和远处转移是相互关联和相互依赖的。外泌体是负责准备前转移龛和肿瘤与远处转移部位之间通讯的关键因素。癌症干细胞 (CSC) 是具有自我更新特性的癌细胞亚群,被认为是转移的原因。本研究旨在了解转移性细胞系衍生的外泌体及其对 CSC 标志物表达的调节对原发性结肠癌细胞系的影响。我们已经确定,用转移性结肠癌细胞衍生的外泌体处理原发性结肠癌细胞系显著增加了增殖、集落形成、细胞迁移和侵袭。此外,外泌体处理后球体的数量和大小也显著增加。我们发现这种转移表型是由于原发性结肠癌细胞中 CD133 和 DCLK1 的表达增加所致。

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