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Cholesterol synthesis is essential for the growth of liver metastasis‐prone colorectal cancer cells.

Authors :
Taniguchi, Kumiko
Sugihara, Kei
Miura, Takashi
Hoshi, Daisuke
Kohno, Susumu
Takahashi, Chiaki
Hirata, Eishu
Kiyokawa, Etsuko
Source :
Cancer Science; Nov2024, Vol. 115 Issue 11, p3817-3828, 12p
Publication Year :
2024

Abstract

Metastasis to the liver is a leading cause of death in patients with colorectal cancer. To investigate the characteristics of cancer cells prone to metastasis, we utilized an isogenic model of BALB/c and colon tumor 26 (C26) cells carrying an active KRAS mutation. Liver metastatic (LM) 1 cells were isolated from mice following intrasplenic transplantation of C26 cells. Subsequent injections of LM1 cells generated LM2 cells, and after four cycles, LM4 cells were obtained. In vitro, using a perfusable capillary network system, we found comparable extravasation frequencies between C26 and LM4 cells. Both cell lines showed similar growth rates in vitro. However, C26 cells showed higher glucose consumption, whereas LM4 cells incorporated more fluorescent fatty acids (FAs). Biochemical analysis revealed that LM4 cells had higher cholesterol levels than C26 cells. A correlation was observed between fluorescent FAs and cholesterol levels detected using filipin III. LM4 cells utilized FAs as a source for cholesterol synthesis through acetyl‐CoA metabolism. In cellular analysis, cholesterol accumulated in punctate regions, and upregulation of NLRP3 and STING proteins, but not mTOR, was observed in LM4 cells. Treatment with a cholesterol synthesis inhibitor (statin) induced LM4 cell death in vitro and suppressed LM4 cell growth in the livers of nude mice. These findings indicate that colorectal cancer cells prone to liver metastasis show cholesterol‐dependent growth and that statin therapy could help treat liver metastasis in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13479032
Volume :
115
Issue :
11
Database :
Complementary Index
Journal :
Cancer Science
Publication Type :
Academic Journal
Accession number :
180655578
Full Text :
https://doi.org/10.1111/cas.16331