Home HOME Neoplasma 2021 Neoplasma Vol.68, No.1, p.71–78, 2021

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.68, No.1, p.71–78, 2021

Title: HMGB1-activated fibroblasts promote breast cancer cells metastasis via RAGE/aerobic glycolysis
Author: Yuanping Chen, Lu Cai, Xiaoqing Guo, Zelei Li, Xiaohong Liao, Xuebing Zhang, Li Huang, Jing He

Abstract: Highly expressed high mobility group box-1 protein (HMGB1) promotes tumor metastasis. Whether HMGB1 participates in breast cancer cell activation of fibroblasts is unknown.
The culture medium of 6 breast cancer cell lines with different migration potential, and with HMGB1 overexpression or knockdown was used to induce fibroblast activation, and collagen and α-SMA expression were measured. We evaluated the migration potential of MDA-MB-231 cells with fibroblasts treated with 3-PO (3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) inhibitor, anti-HMGB1 treatment, or RAGE (receptor for advanced glycation end products) knockdown. A lung metastasis murine model was used to evaluate whether the RAGE-knockdown fibroblasts mitigates MDA-MB-231 metastasis.
Breast cancer cells that are highly migratory and have a high invasive potential, had higher HMGB1 expression and induced greater fibroblast activation strongly than cells with poorer motility. hrHMGB1 and the supernatants of HMGB1-overexpressed MCF-7 cells promoted fibroblast activation, but loss-HMGB1 of MDA-MB-231 abolished potential. Moreover, a novel mechanism was identified by which HMGB1 facilitated fibroblast activation by RAGE/aerobic glycolysis. Consistently, fibroblasts enhanced MDA-MB-231 metastasis, but the enhancement was reversed by 3-PO inhibition, anti-HMGB1 treatment, or RAGE knockdown in vitro and in vivo.
We identified that HMGB1 secreted by breast cancer cells promotes fibroblast activation via RAGE/aerobic glycolysis, and activated fibroblasts enhance breast cancer cell metastasis through increased lactate.

Keywords: breast cancer cells; fibroblast; high mobility group box-1 protein; RAGE; aerobic glycolysis
Published online: 08-Oct-2020
Year: 2021, Volume: 68, Issue: 1 Page From: 71, Page To: 78

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