Reciprocal signaling and direct physical interactions between fibroblasts and breast cancer cells in a 3D environment
| العنوان: | Reciprocal signaling and direct physical interactions between fibroblasts and breast cancer cells in a 3D environment |
|---|---|
| المؤلفون: | Thomas P. Conway, Kayla Conway, Edward Voss, Suchaeta V. Hegde, Nikash Pradhan, Megan A. Klepitsch, David R. Soll, Karla J. Daniels, Yang-Nim Park, Deborah Wessels, Daniel F. Lusche |
| المصدر: | PLoS ONE, Vol 14, Iss 6, p e0218854 (2019) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cellular pathology, Molecular biology, Gene Expression, Cell Communication, Biochemistry, 0302 clinical medicine, Fibroblast activation protein, alpha, Cancer-Associated Fibroblasts, Cell Movement, Animal Cells, Breast Tumors, Tumor Microenvironment, Medicine and Health Sciences, PDPN, Cell Aggregation, Connective Tissue Cells, Multidisciplinary, Membrane Glycoproteins, Chemistry, Cell aggregation, Cell biology, Drug Combinations, Cell Motility, medicine.anatomical_structure, Oncology, Connective Tissue, Cell Processes, 030220 oncology & carcinogenesis, Medicine, Female, Proteoglycans, Collagen, Cellular Types, Anatomy, Signal Transduction, Research Article, Cell signaling, Science, Breast Neoplasms, DNA construction, Models, Biological, 03 medical and health sciences, Cell Line, Tumor, Spheroids, Cellular, Breast Cancer, medicine, Genetics, Humans, Fibroblast, Cell Shape, Matrigel, Biology and Life Sciences, Proteins, Cancers and Neoplasms, Cell Biology, Fibroblasts, Chemokine CXCL12, Coculture Techniques, Matrix Metalloproteinases, Research and analysis methods, 030104 developmental biology, Biological Tissue, Molecular biology techniques, Culture Media, Conditioned, Cancer cell, Plasmid Construction, Laminin, Collagens |
| الوصف: | Tumorigenic cells undergo cell aggregation and aggregate coalescence in a 3D Matrigel environment. Here, we expanded this 3D platform to assess the interactions of normal human dermal fibroblasts (NHDFs) and human primary mammary fibroblasts (HPMFs) with breast cancer-derived, tumorigenic cells (MDA-MB-231). Medium conditioned by MDA-MB-231 cells activates both types of fibroblasts, imbuing them with the capacity to accelerate the rate of aggregation and coalescence of MDA-MB-231 cells more than four fold. Acceleration is achieved 1) by direct physical interactions with MDA-MB-231 cells, in which activated fibroblasts penetrate the MDA-MB-231/Matrigel 3D environment and function as supporting scaffolds for MDA-MB-231 aggregation and coalescence, and 2) through the release of soluble accelerating factors, including matrix metalloproteinase (MMPs) and, in the case of activated NHDFs, SDF-1α/CXCL12. Fibroblast activation includes changes in morphology, motility, and gene expression. Podoplanin (PDPN) and fibroblast activation protein (FAP) are upregulated by more than nine-fold in activated NHDFs while activated HPMFs upregulate FAP, vimentin, desmin, platelet derived growth factor receptor A and S100A4. Overexpression of PDPN, but not FAP, in NHDF cells in the absence of MDA-MB-231-conditioned medium, activates NHDFs. These results reveal that complex reciprocal signaling between fibroblasts and cancer cells, coupled with their physical interactions, occurs in a highly coordinated fashion that orchestrates aggregation and coalescence, behaviors specific to cancer cells in a 3D environment. These in vitro interactions may reflect events involved in early tumorigenesis, particularly in cases of field cancerization, and may represent a new mechanism whereby cancer-associated fibroblasts (CAFs) promote tumor growth. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00c218e6722125c85c401f52ee0f0035 https://doaj.org/article/09bea94a3ce04961ab0abb6fe31c2a55 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....00c218e6722125c85c401f52ee0f0035 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|