Fibronectin regulation of integrin b1 and slug in circulating tumor cells

Jeannette Huaman, Michelle Naidoo, Xingxing Zang, Olorunseun O. Ogunwobi

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Article number618
JournalCells
Volume8
Issue number6
DOIs
StatePublished - 2019

Keywords

  • Castration resistant prostate cancer (CRPC)
  • Circulating tumor cells (CTCs)
  • Epithelial-to-mesenchymal transition (EMT)
  • Fibronectin
  • Hepatocellular carcinoma (HCC)
  • Immunomodulation
  • Integrin B1
  • Major histocompatibility complex class I (MHCI)
  • Metastasis
  • SLUG

ASJC Scopus subject areas

  • Medicine(all)

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