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

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.

Keywords: CD133; Cancer stem cell markers; DCLK1; Exosomes.

MeSH terms

  • AC133 Antigen / genetics
  • AC133 Antigen / metabolism
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / genetics
  • Doublecortin-Like Kinases / genetics
  • Doublecortin-Like Kinases / metabolism
  • Exosomes*
  • Extracellular Vesicles*
  • Humans
  • Neoplastic Stem Cells / metabolism
  • Protein Serine-Threonine Kinases / genetics

Substances

  • DCLK1 protein, human
  • Doublecortin-Like Kinases
  • Protein Serine-Threonine Kinases
  • AC133 Antigen