Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stroma

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dc.citation.articleNumber1271en_US
dc.citation.issueNumber9en_US
dc.citation.journalTitleBiologyen_US
dc.citation.volumeNumber11en_US
dc.contributor.authorSablatura, Lindsey K.en_US
dc.contributor.authorTellman, Tristen V.en_US
dc.contributor.authorKim, Aeminen_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.date.accessioned2022-10-28T17:43:03Zen_US
dc.date.available2022-10-28T17:43:03Zen_US
dc.date.issued2022en_US
dc.description.abstractThe bone marrow tumor microenvironment (BMTE) is a complex network of cells, extracellular matrix, and sequestered signaling factors that initially act as a hostile environment for disseminating tumor cells (DTCs) from the cancerous prostate. Three-dimensional (3D) culture systems offer an opportunity to better model these complex interactions in reactive stroma, providing contextual behaviors for cancer cells, stromal cells, and endothelial cells. Using a new system designed for the triculture of osteoblastic prostate cancer (PCa) cells, stromal cells, and microvascular endothelial cells, we uncovered a context-specific pro-apoptotic effect of endothelial cells of the bone marrow different from those derived from the lung or dermis. The paracrine nature of this effect was demonstrated by observations that conditioned medium from bone marrow endothelial cells, but not from dermal or lung endothelial cells, led to PCa cell death in microtumors grown in 3D BMTE-simulating hydrogels. Analysis of the phosphoproteome by reverse phase protein analysis (RPPA) of PCa cells treated with conditioned media from different endothelial cells identified the differential regulation of pathways involved in proliferation, cell cycle regulation, and apoptosis. The findings from the RPPA were validated by western blotting for representative signaling factors identified, including forkhead box M1 (FOXM1; proliferation factor), pRb (cell cycle regulator), and Smac/DIABLO (pro-apoptosis) among treatment conditions. The 3D model presented here thus presents an accurate model to study the influence of the reactive BMTE, including stromal and endothelial cells, on the adaptive behaviors of cancer cells modeling DTCs at sites of bone metastasis. These findings in 3D culture systems can lead to a better understanding of the real-time interactions among cells present in reactive stroma than is possible using animal models.en_US
dc.identifier.citationSablatura, Lindsey K., Tellman, Tristen V., Kim, Aemin, et al.. "Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stroma." <i>Biology,</i> 11, no. 9 (2022) MDPI: https://doi.org/10.3390/biology11091271.en_US
dc.identifier.digitalbiology-11-01271-v2en_US
dc.identifier.doihttps://doi.org/10.3390/biology11091271en_US
dc.identifier.urihttps://hdl.handle.net/1911/113768en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleBone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stromaen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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