Reciprocal signaling and direct physical interactions between fibroblasts and breast cancer cells in a 3D environment.

Autor: Wessels DJ; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Pradhan N; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Park YN; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Klepitsch MA; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Lusche DF; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Daniels KJ; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Conway KD; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Voss ER; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Hegde SV; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Conway TP; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America., Soll DR; Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jun 24; Vol. 14 (6), pp. e0218854. Date of Electronic Publication: 2019 Jun 24 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0218854
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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