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A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration
SIMPLE SUMMARY: Recent advances in 3D cell culture have provided new opportunities for investigating interactions between cancer cells and their surrounding stromal cells. The 3D culture platform described herein is both time efficient and economical in the study of direct cell–cell interactions. Th...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600195/ https://www.ncbi.nlm.nih.gov/pubmed/33049958 http://dx.doi.org/10.3390/biology9100328 |
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author | Zhang, Yihe Jiang, Bingjie Lee, Meng Huee |
author_facet | Zhang, Yihe Jiang, Bingjie Lee, Meng Huee |
author_sort | Zhang, Yihe |
collection | PubMed |
description | SIMPLE SUMMARY: Recent advances in 3D cell culture have provided new opportunities for investigating interactions between cancer cells and their surrounding stromal cells. The 3D culture platform described herein is both time efficient and economical in the study of direct cell–cell interactions. The unique design of our dumbbell model had allowed us to visualize and monitor the entire recruitment process of cancer cells by fibroblasts under an in vitro condition. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction. ABSTRACT: Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast–tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction. |
format | Online Article Text |
id | pubmed-7600195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76001952020-11-01 A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration Zhang, Yihe Jiang, Bingjie Lee, Meng Huee Biology (Basel) Article SIMPLE SUMMARY: Recent advances in 3D cell culture have provided new opportunities for investigating interactions between cancer cells and their surrounding stromal cells. The 3D culture platform described herein is both time efficient and economical in the study of direct cell–cell interactions. The unique design of our dumbbell model had allowed us to visualize and monitor the entire recruitment process of cancer cells by fibroblasts under an in vitro condition. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction. ABSTRACT: Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast–tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction. MDPI 2020-10-08 /pmc/articles/PMC7600195/ /pubmed/33049958 http://dx.doi.org/10.3390/biology9100328 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Yihe Jiang, Bingjie Lee, Meng Huee A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title | A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title_full | A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title_fullStr | A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title_full_unstemmed | A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title_short | A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration |
title_sort | novel 3d model for visualization and tracking of fibroblast-guided directional cancer cell migration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600195/ https://www.ncbi.nlm.nih.gov/pubmed/33049958 http://dx.doi.org/10.3390/biology9100328 |
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