Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells. Academic Article uri icon

Overview

abstract

  • Metastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these models, novel primary tumor and CTC cell lines were established. CTCs exhibited greater migration than primary tumor-derived cells, as well as epithelial-to-mesenchymal transition (EMT), as observed from decreased E-cadherin and increased SLUG and fibronectin expression. Additionally, when fibronectin was knocked down in CTCs, integrin B1 and SLUG were decreased, indicating regulation of these molecules by fibronectin. Investigation of cell surface molecules and secreted cytokines conferring immunomodulatory advantage to CTCs revealed decreased major histocompatibility complex class I (MHCI) expression and decreased endostatin, C-X-C motif chemokine 5 (CXCL5), and proliferin secretion by CTCs. Taken together, these findings indicate that CTCs exhibit distinct characteristics from primary tumor-derived cells. Furthermore, CTCs demonstrate enhanced migration in part through fibronectin regulation of integrin B1 and SLUG. Further study of CTC biology will likely uncover additional important mechanisms of cancer metastasis.

publication date

  • June 20, 2019

Research

keywords

  • Fibronectins
  • Integrin beta1
  • Neoplastic Cells, Circulating
  • Snail Family Transcription Factors

Identity

PubMed Central ID

  • PMC6627780

Scopus Document Identifier

  • 84886044680

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-13-0602

PubMed ID

  • 31226820

Additional Document Info

volume

  • 8

issue

  • 6