Journal article
Reciprocal signaling and direct physical interactions between fibroblasts and breast cancer cells in a 3D environment
PloS one, Vol.14(6), pp.e0218854-e0218854
06/24/2019
DOI: 10.1371/journal.pone.0218854
PMCID: PMC6590889
PMID: 31233557
Abstract
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.
Details
- Title: Subtitle
- Reciprocal signaling and direct physical interactions between fibroblasts and breast cancer cells in a 3D environment
- Creators
- Deborah J Wessels - Developmental Studies Hybridoma BankNikash Pradhan - Developmental Studies Hybridoma BankYang-Nim Park - Developmental Studies Hybridoma BankMegan A Klepitsch - Developmental Studies Hybridoma BankDaniel F Lusche - Developmental Studies Hybridoma BankKarla J Daniels - Developmental Studies Hybridoma BankKayla D Conway - Developmental Studies Hybridoma BankEdward R Voss - Developmental Studies Hybridoma BankSuchaeta V Hegde - Developmental Studies Hybridoma BankThomas P Conway - Developmental Studies Hybridoma BankDavid R Soll - Developmental Studies Hybridoma Bank
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.14(6), pp.e0218854-e0218854
- DOI
- 10.1371/journal.pone.0218854
- PMID
- 31233557
- PMCID
- PMC6590889
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Alternative title
- Activated fibroblasts stimulate 3D cancer cell coalescence by physical interactions and reciprocal signaling
- Language
- English
- Date published
- 06/24/2019
- Academic Unit
- Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9984230629202771
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