In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types

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dc.creatorMatossian, M. D.
dc.creatorChang, T.
dc.creatorWright, M. K.
dc.creatorBurks, H. E.
dc.creatorElliott, S.
dc.creatorSabol, R. A.
dc.creatorWathieu, H.
dc.creatorWindsor, G. O.
dc.creatorAlzoubi, Madlin S.
dc.creatorKing, C. T.
dc.creatorBursavich, J. B.
dc.creatorHam, A. M.
dc.creatorSavoie, J. J.
dc.creatorNguyen, K.
dc.creatorBaddoo, M.
dc.creatorFlemington, E.
dc.creatorSirenko, O.
dc.creatorCromwell, E. F.
dc.creatorHebert, K. L.
dc.creatorLau, F.
dc.creatorIzadpanah, R.
dc.creatorBrown, H.
dc.creatorSinha, S.
dc.creatorZabaleta, J.
dc.creatorRiker, A. I.
dc.creatorMoroz, K.
dc.creatorMiele, L.
dc.creatorZea, A. H.
dc.creatorOchoa, A.
dc.creatorBunnell, Bruce A.
dc.creatorCollins-Burow, B. M.
dc.creatorMartin, E. C.
dc.creatorBurow, Matthew E.
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2022-08-25T15:39:45Z
dc.date.available2022-08-25T15:39:45Z
dc.date.issued2021-08-09
dc.description.abstractMetaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu.MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell-matrix interactions in rare cancer types using higher passage PDX tissue.
dc.description.sponsorshipThis work was supported by grants from National Institute of Health (NIH) (Grants No. R01-CA125806-04 (MEB), 1R15CA176496-01A1 (MEB) and R01-CA174785-A1 (BMC-B)). This work was also supported in part by U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessarily represent the ofcial views of the National Institutes of Health.
dc.identifier.citationMatossian, M. D., Chang, T., Wright, M. K., Burks, H. E., Elliott, S., Sabol, R. A., Wathieu, H., Windsor, G. O., Alzoubi, M. S., King, C. T., Bursavich, J. B., Ham, A. M., Savoie, J. J., Nguyen, K., Baddoo, M., Flemington, E., Sirenko, O., Cromwell, E. F., Hebert, K. L., Lau, F., ... Burow, M. E. (2022). In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 24(1), 127-144. https://doi.org/10.1007/s12094-021-02677-8
dc.identifier.issn1699-3055
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31647
dc.identifier.volume24
dc.publisherSpringer
dc.relation.urihttps://doi.org/10.1007/s12094-021-02677-8
dc.rights.holder© The Author(s) 2021
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceClinical and Translational Oncology
dc.subjectCollagen
dc.subjectExtracellular matrix
dc.subjectMetaplastic breast carcinoma
dc.subjectPatient-derived xenograft
dc.subjectTriple negative breast cancer
dc.subject.meshBone Marrow Cells / immunology
dc.subject.meshBone Marrow Cells / metabolism
dc.subject.meshCell Culture Techniques
dc.subject.meshCell Differentiation
dc.subject.meshCells, Cultured
dc.subject.meshCytokines / genetics
dc.subject.meshCytokines / metabolism
dc.subject.meshEukaryotic Initiation Factor-2 / metabolism
dc.subject.meshHumans
dc.subject.meshImmunomodulation
dc.subject.meshImmunophenotyping
dc.subject.meshInflammation Mediators / metabolism
dc.subject.meshMesenchymal Stem Cells / immunology
dc.subject.meshMesenchymal Stem Cells / metabolism
dc.subject.meshRegenerative Medicine
dc.subject.meshSequence Analysis, RNA
dc.subject.meshSignal Transduction
dc.subject.meshTranscriptomeBone Marrow Cells / immunology
dc.subject.meshBone Marrow Cells / metabolism
dc.subject.meshCell Culture Techniques
dc.subject.meshCell Differentiation
dc.subject.meshCells, Cultured
dc.subject.meshCytokines / genetics
dc.subject.meshCytokines / metabolism
dc.subject.meshEukaryotic Initiation Factor-2 / metabolism
dc.subject.meshHumans
dc.subject.meshImmunomodulation
dc.subject.meshImmunophenotyping
dc.subject.meshInflammation Mediators / metabolism
dc.subject.meshMesenchymal Stem Cells / immunology
dc.subject.meshMesenchymal Stem Cells / metabolism
dc.subject.meshRegenerative Medicine
dc.subject.meshSequence Analysis, RNA
dc.subject.meshSignal Transduction
dc.subject.meshTranscriptome
dc.titleIn-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types
dc.typeArticle
dc.type.materialtext

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