Suetsugu Atsushi, Hiroshima Yukihiko, Matsumoto Takuro, Hasagawa Kosuke, Nakamura Miki, Shimizu Masahito, Saji Shigetoyo, Moriwaki Hisataka, Bouvet Michael, Hoffman Robert M
Gifu University Graduate School of Medicine, Gifu, Japan AntiCancer, Inc. San Diego, CA, U.S.A Department of Surgery, University of California, San Diego, CA, U.S.A.
AntiCancer, Inc. San Diego, CA, U.S.A Department of Surgery, University of California, San Diego, CA, U.S.A.
Anticancer Res. 2015 Nov;35(11):5821-5.
BACKGROUND/AIM: The tumor microenvironment (TME) is critical for tumor growth and progression. We report here an imageable model of the TME of orthotopic liver cancer.
The transgenic red fluorescent protein (RFP)-expressing nude mouse was used as the host. The RFP nude mouse expresses RFP in all organs. Non-colored Huh-7 human hepatoma cells were injected in the spleen of RFP nude mice to establish an orthotopic liver cancer model. TME formation resulting from the orthotopic liver tumor was observed using the Olympus OV100 small animal fluorescence imaging system.
Non-colored liver cancer cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. RFP-expressing host cells and blood vessels were recruited by the liver tumors as visualized by fluorescence imaging. A desmin- and sirus-red-positive area increased around and within the liver tumor over time.
These results indicate cancer-associated fibroblasts (CAFs) were recruited by the liver tumors suggesting that CAFs, along with the angiogenic tumor blood vessels, were necessary for liver-tumor growth and could serve as visible therapeutic targets.
背景/目的:肿瘤微环境(TME)对肿瘤的生长和进展至关重要。我们在此报告一种原位肝癌TME的可成像模型。
将表达转基因红色荧光蛋白(RFP)的裸鼠作为宿主。该RFP裸鼠在所有器官中均表达RFP。将未染色的Huh-7人肝癌细胞注射到RFP裸鼠的脾脏中,以建立原位肝癌模型。使用奥林巴斯OV100小动物荧光成像系统观察原位肝肿瘤形成的TME。
将细胞移植到脾脏28天后,未染色的肝癌细胞在肝脏中形成肿瘤集落。通过荧光成像可见,表达RFP的宿主细胞和血管被肝肿瘤募集。随着时间的推移,在肝肿瘤周围和内部,结蛋白和天狼星红阳性区域增加。
这些结果表明肝肿瘤募集了癌症相关成纤维细胞(CAF),提示CAF与血管生成性肿瘤血管一起,对肝肿瘤生长是必需的,并且可作为可见的治疗靶点。