TY - JOUR
T1 - Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy
AU - Malone, Marie K.
AU - Smrekar, Karly
AU - Park, Sunju
AU - Blakely, Brianna
AU - Walter, Alec
AU - Nasta, Nicholas
AU - Park, Jay
AU - Considine, Michael
AU - Danilova, Ludmila V.
AU - Pandey, Niranjan B.
AU - Fertig, Elana J.
AU - Popel, Aleksander S.
AU - Jin, Kideok
N1 - Funding Information:
This work was supported by startup funding from Albany College of Pharmacy and Health Sciences, the National Institutes of Health grant R01 CA138264 and P30 CA006973.
Publisher Copyright:
© 2020, © 2020 Taylor & Francis Group, LLC.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - In 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.
AB - In 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.
KW - TNBC
KW - secreted factors
KW - stromal cells
KW - tumor microenvironment
KW - secretome
UR - http://www.scopus.com/inward/record.url?scp=85082454918&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082454918&partnerID=8YFLogxK
U2 - 10.1080/15384047.2020.1739484
DO - 10.1080/15384047.2020.1739484
M3 - Article
C2 - 32213106
AN - SCOPUS:85082454918
SN - 1538-4047
VL - 21
SP - 560
EP - 569
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 6
ER -