Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells.

Autor:	DeCastro AJL; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States., Pranda MA; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States., Gray KM; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States., Merlo-Coyne J; Department of Biology, University of Maryland, College Park, MD, United States., Girma N; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States., Hurwitz M; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States., Zhang Y; Department of Epidemiology and Public Health, University of Maryland, Baltimore, MD, United States.; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, United States., Stroka KM; Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States.; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, United States.; Biophysics Program, University of Maryland, College Park, MD, United States.; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Feb 17; Vol. 10, pp. 790410. Date of Electronic Publication: 2022 Feb 17 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.790410
Abstrakt:	Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts aiming to help predict metastatic propensities to organ-specific sites in a clinical setting. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 DeCastro, Pranda, Gray, Merlo-Coyne, Girma, Hurwitz, Zhang and Stroka.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu