| Title: |
Role of Epiregulin on Lipopolysaccharide-Induced Hepatocarcinogenesis as a Mediator via EGFR Signaling in the Cancer Microenvironment. |
| Authors: |
Kubo, Takahiro, Nishimura, Norihisa, Kaji, Kosuke, Tomooka, Fumimasa, Shibamoto, Akihiko, Iwai, Satoshi, Suzuki, Junya, Kawaratani, Hideto, Namisaki, Tadashi, Akahane, Takemi, Yoshiji, Hitoshi |
| Source: |
International Journal of Molecular Sciences; Apr2024, Vol. 25 Issue 8, p4405, 17p |
| Subject Terms: |
TUMOR microenvironment, REVERSE transcriptase polymerase chain reaction, EPIDERMAL growth factor receptors, EPIDERMAL growth factor, LIVER cells |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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