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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4414

Title: Role of Epiregulin on Lipopolysaccharide-Induced Hepatocarcinogenesis as a Mediator via EGFR Signaling in the Cancer Microenvironment
Other Titles: がん微小環境におけるEGFRシグナルを介したメディエーターとしての肝発がんに対するエピレグリンの役割
Authors: Kubo, Takahiro
Nishimura, Norihisa
Kaji, Kosuke
Tomooka, Fumimasa
Shibamoto, Akihiko
Iwai, Satoshi
Suzuki, Junya
Kawaratani, Hideto
Namisaki, Tadashi
Akahane, Takemi
Yoshiji, Hitoshi
Keywords: epiregulin
interleukin-8
lipopolysaccharides
tumor angiogenesis
tumor microenvironment
Issue Date: Apr-2024
Publisher: MDPI
Citation: International Journal of Molecular Sciences. 2024 Apr, vol.25, no.8, article no.4405
Abstract: Lipopolysaccharides (LPSs) have been reported to be important factors in promoting the progression of hepatocellular carcinoma (HCC), but the corresponding molecular mechanisms remain to be elucidated. We hypothesize that epiregulin (EREG), an epidermal growth factor (EGF) family member derived from hepatic stellate cells (HSCs) and activated by LPS stimulation, is a crucial mediator of HCC progression with epidermal growth factor receptor (EGFR) expression in the tumor microenvironment. We used a mouse xenograft model of Huh7 cells mixed with half the number of LX-2 cells, with/without intraperitoneal LPS injection, to elucidate the role of EREG in LPS-induced HCC. In the mouse model, LPS administration significantly enlarged the size of xenografted tumors and elevated the expression of EREG in tumor tissues compared with those in negative controls. Moreover, CD34 immunostaining and the gene expressions of angiogenic markers by a reverse transcription polymerase chain reaction revealed higher vascularization, with increased interleukin-8 (IL-8) expression in the tumors of the mice group treated with LPS compared to those without LPS. Our data collectively suggested that EREG plays an important role in the cancer microenvironment under the influence of LPS to increase not only the tumor cell growth and migration/invasion of EGFR-positive HCC cells but also tumor neovascularization via IL-8 signaling.
Description: 権利情報:© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/10564/4414
ISSN: 1661-6596
DOI: https://doi.org/10.3390/ijms25084405
Academic Degrees and number: 24601甲第938号
Degree-granting date: 2024-12-26
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2024年度

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