Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy.

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dc.contributor.authorMalone, Marie K*
dc.contributor.authorSmrekar, Karly*
dc.contributor.authorPark, Sunju
dc.contributor.authorBlakely, Brianna*
dc.contributor.authorWalter, Alec*
dc.contributor.authorNasta, Nicholas*
dc.contributor.authorPark, Jay*
dc.contributor.authorConsidine, Michael
dc.contributor.authorDanilova, Ludmila V
dc.contributor.authorPandey, Niranjan B
dc.contributor.authorFertig, Elana J
dc.contributor.authorPopel, Aleksander S
dc.contributor.authorJin, Kideok
dc.contributor.orcidhttps://orcid.org/0000-0001-6898-2512
dc.date.accessioned2023-11-29T18:52:33Z
dc.date.available2023-11-29T18:52:33Z
dc.date.issued6/2/2020
dc.description.abstractIn triple-negative breast cancer (TNBC), the lack of therapeutic markers and effective targeted therapies result in an incurable metastatic disease associated with a poor prognosis. Crosstalks within the tumor microenvironment (TME), including those between cancer and stromal cells, affect the tumor heterogeneity, growth, and metastasis. Previously, we have demonstrated that IL-6, IL-8, and CCL5 play a significant role in TNBC growth and metastasis. In this study, we performed a systematic analysis of cytokine factors secreted from four stromal components (fibroblasts, macrophages, lymphatic endothelial cells, and blood microvascular endothelial cells) induced by four TNBC cell types. Through bioinformatic analysis, we selected putative candidates of secreted factors from stromal cells, which are involved in EMT activity, cell proliferation, metabolism, and matrisome pathways. Among the candidates, LCN2, GM-CSF, CST3, IL-6, IL-8, and CHI3L1 are ranked highly. Significantly, Lipocalin-2 (LCN2) is upregulated in the crosstalk of stromal cells and four different TNBC cells. We validated the increase of LCN2 secreted from four stromal cells induced by TNBC cells. Using a specific LCN2 antibody, we observed the inhibition of TNBC cell growth and migration. Taken together, these results propose secreted factors as molecular targets to treat TNBC progression via crosstalk with stromal components.
dc.description.grantGrant Funded
dc.description.sponsorshipR01 CA138264/CA/NCI NIH HHS/United States
dc.description.urihttps://doi.org/10.1080/15384047.2020.1739484
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc7515526/
dc.identifier.citationMalone MK, Smrekar K, Park S, Blakely B, Walter A, Nasta N, Park J, Considine M, Danilova LV, Pandey NB, Fertig EJ, Popel AS, Jin K. Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy. Cancer Biol Ther. 2020 Jun 2;21(6):560-569. doi: 10.1080/15384047.2020.1739484. Epub 2020 Mar 26. PMID: 32213106; PMCID: PMC7515526.
dc.identifier.issn1538-4047
dc.identifier.other32213106
dc.identifier.urihttps://hdl.handle.net/20.500.14303/430
dc.language.isoen
dc.publisherTaylor & Francis
dc.relation.ispartofCancer Biology & Therapy
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectTNBC
dc.subjectsecreted factors
dc.subjectstromal cells
dc.subjecttumor microenvironment
dc.subjectsecretome
dc.titleCytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy.
dc.typeArticle
local.departmentprogramDepartment of Pharmaceutical Sciences
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