Phenotypic heterogeneity and plasticity of cancer cell migration in a pancreatic tumor three-dimensional culture model

Seul Ki Kim, So Dam Jang, Hyunho Kim, Seok Chung, Jong Kook Park, Hyo Jeong Kuh

Research output: Contribution to journalArticle

Abstract

Invasive cancer cell migration is a key feature of metastatic human pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms remain poorly understood. Here, we investigated modes of cancer cell invasion using two pancreatic cancer cell lines with differential epithelial–mesenchymal status, PANC-1 and BxPC-3, under 3D culture conditions. Multicellular tumor spheroids (TSs) were grown in a collagen matrix co-cultured with pancreatic stellate cells (PSCs) using microchannel chips. PANC-1 cells showed individual migration from TSs via invadopodium formation. BxPC-3 cells showed plasticity between collective and individual migration in either mesenchymal mode, with filopodium-like protrusions, or blebby amoeboid mode. These two cell lines showed significantly different patterns of extracellular matrix (ECM) remodeling, with MMP-dependent degradation in a limited area of ECM around invadopodia for PANC-1 cells, or MMP-independent extensive deformation of ECM for BxPC-3 cells. Cancer cell migration out of the collagen channel significantly increased by PSCs and directional cancer cell migration was mediated by fibronectin deposited by PSCs. Our results highlight the phenotypic heterogeneity and plasticity of PDAC cell migration and ECM remodeling under 3D culture conditions. This 3D co-culture model of pancreatic cancer cells and PSCs offers a useful tool for studying cancer cell migration and ECM remodeling to identify and develop potential molecular targets and anti-cancer agents against human PDAC.

Original languageEnglish
Article number1305
JournalCancers
Volume12
Issue number5
DOIs
Publication statusPublished - 2020 May

Keywords

  • 3D co-culture
  • ECM remodeling
  • Migration
  • Pancreatic cancer
  • Tumor spheroids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phenotypic heterogeneity and plasticity of cancer cell migration in a pancreatic tumor three-dimensional culture model'. Together they form a unique fingerprint.

  • Cite this