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Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor
dc.contributor.authorNovak, Caymen M.
dc.contributor.authorHorst, Eric N.
dc.contributor.authorTaylor, Charles C.
dc.contributor.authorLiu, Catherine Z.
dc.contributor.authorMehta, Geeta
dc.date.accessioned2019-10-30T15:29:37Z
dc.date.availableWITHHELD_14_MONTHS
dc.date.available2019-10-30T15:29:37Z
dc.date.issued2019-11
dc.identifier.citationNovak, Caymen M.; Horst, Eric N.; Taylor, Charles C.; Liu, Catherine Z.; Mehta, Geeta (2019). "Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor." Biotechnology and Bioengineering 116(11): 3084-3097.
dc.identifier.issn0006-3592
dc.identifier.issn1097-0290
dc.identifier.urihttps://hdl.handle.net/2027.42/151824
dc.description.abstractBreast cancer cells experience a range of shear stresses in the tumor microenvironment (TME). However most current in vitro three‐dimensional (3D) models fail to systematically probe the effects of this biophysical stimuli on cancer cell metastasis, proliferation, and chemoresistance. To investigate the roles of shear stress within the mammary and lung pleural effusion TME, a bioreactor capable of applying shear stress to cells within a 3D extracellular matrix was designed and characterized. Breast cancer cells were encapsulated within an interpenetrating network hydrogel and subjected to shear stress of 5.4 dynes cm−2 for 72 hr. Finite element modeling assessed shear stress profiles within the bioreactor. Cells exposed to shear stress had significantly higher cellular area and significantly lower circularity, indicating a motile phenotype. Stimulated cells were more proliferative than static controls and showed higher rates of chemoresistance to the anti‐neoplastic drug paclitaxel. Fluid shear stress‐induced significant upregulation of the PLAU gene and elevated urokinase activity was confirmed through zymography and activity assay. Overall, these results indicate that pulsatile shear stress promotes breast cancer cell proliferation, invasive potential, chemoresistance, and PLAU signaling.A shear stress bioreactor was used to apply 3D shear stress stimulus to breast cancer cell lines encapsulated within an interpenetrating network hydrogel. Stimulated cells showed enhanced cellular area, elongation, proliferation, chemoresistance, and upregulation of PLAU and its consequential protein urokinase plasminogen activator (uPA). These results demonstrate the importance of mechanical stimulation consideration within the cancer microenvironment when investigating treatment potentials and chemotherapeutic effectiveness.
dc.publisherWiley Periodicals, Inc.
dc.subject.othershear stress
dc.subject.other3D bioreactor
dc.subject.otherinterpenetrating hydrogel
dc.subject.othermechanotransduction
dc.subject.otherPLAU
dc.subject.otherbreast cancer
dc.titleFluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelBiological Chemistry
dc.subject.hlbsecondlevelEcology and Evolutionary Biology
dc.subject.hlbsecondlevelMathematics
dc.subject.hlbsecondlevelNatural Resources and Environment
dc.subject.hlbsecondlevelStatistics and Numeric Data
dc.subject.hlbsecondlevelPublic Health
dc.subject.hlbtoplevelScience
dc.subject.hlbtoplevelSocial Sciences
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/151824/1/bit27119.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/151824/2/bit27119_am.pdf
dc.identifier.doi10.1002/bit.27119
dc.identifier.sourceBiotechnology and Bioengineering
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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