Cancers, Vol. 12, Pages 1305: Phenotypic Heterogeneity and Plasticity of Cancer Cell Migration in a Pancreatic Tumor Three-Dimensional Culture Model

Cancers, Vol. 12, Pages 1305: Phenotypic Heterogeneity and Plasticity of Cancer Cell Migration in a Pancreatic Tumor Three-Dimensional Culture Model Cancers doi: 10.3390/cancers12051305 Authors: Seul-Ki Kim So Dam Jang Hyunho Kim Seok Chung Jong Kook Park Hyo-Jeong Kuh 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 phenot...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research