Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Role of Epiregulin on Lipopolysaccharide-Induced Hepatocarcinogenesis as a Mediator in the Cancer Microenvironment

Takahiro Kubo
,
Norihisa Nishimura
* ORCID logo ,
Kosuke Kaji
,
Fumimasa Tomooka
,
Akihiko Shibamoto
,
Satoshi Iwai
ORCID logo ,
Junya Suzuki
,
Hideto Kawaratani
ORCID logo ,
Tadashi Namisaki
ORCID logo ,
Takemi Akahane
ORCID logo ,
Hitoshi Yoshiji
Version 1 : Received: 2 January 2024 / Approved: 3 January 2024 / Online: 3 January 2024 (23:54:24 CET)

How to cite: Kubo, T.; Nishimura, N.; Kaji, K.; Tomooka, F.; Shibamoto, A.; Iwai, S.; Suzuki, J.; Kawaratani, H.; Namisaki, T.; Akahane, T.; Yoshiji, H. Role of Epiregulin on Lipopolysaccharide-Induced Hepatocarcinogenesis as a Mediator in the Cancer Microenvironment. Preprints 2024, 2024010283. https://doi.org/10.20944/preprints202401.0283.v1 Kubo, T.; Nishimura, N.; Kaji, K.; Tomooka, F.; Shibamoto, A.; Iwai, S.; Suzuki, J.; Kawaratani, H.; Namisaki, T.; Akahane, T.; Yoshiji, H. Role of Epiregulin on Lipopolysaccharide-Induced Hepatocarcinogenesis as a Mediator in the Cancer Microenvironment. Preprints 2024, 2024010283. https://doi.org/10.20944/preprints202401.0283.v1

Abstract

Lipopolysaccharides (LPS) 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 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 reverse transcription polymerase chain reaction revealed higher vascularization, with increased 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 tumor cell growth and migration/invasion of HCC cells but also tumor neovascularization via IL-8 signaling.

Keywords

Epiregulin; Tumor microenvironment; Lipopolysaccharides; Interleukin-8; Tumor angiogenesis

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This 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.

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