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Hua Yang, Shanshan Tan, Hans E Grossniklaus, Vanessa Marie Morales, Qing Zhang, Barry L Burgess, Dan-Ning Hu, Scott E Woodman, Tara A McCannel, Jenny Yang; CXCR4 expression in an intraocular melanoma mouse model with hepatic metastases. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1254.
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© ARVO (1962-2015); The Authors (2016-present)
Tumor cell CXCR4 expression is an associated risk factor for metastasis. The purpose of this study is to characterize CXCR4 expression in intraocular melanoma and its hepatic metastases in a mouse model and image hepatic metastases using MRI with a novel designed CXCR4-targeted contrast agent (ProCA32-CXCR4)
5 different human uveal melanoma cell lines, M20-09-196, M20-07-070, 92.1, OMM3 and Mel290 were evaluated by flow cytometry for the level of CXCR4. Nude mice were inoculated intraocularly with these 5 cell lines. CXCR4 expression was analyzed by immunohistochemistry (IHC) in ocular and hepatic tissues. To understand whether host deficient immune system affect CXCR4 expression in tumors, ocular and hepatic tissues from strains of mice (C57BL/6 with or without anti-asialo GM1, DBA/2J, DBA/2J.Gpnmb+ and BXD102) inoculated in our well-established intraocular mouse melanoma model system were evaluated by IHC as well. The abdomen of mice inoculated M20-09-196 was scanned by MRI at 30 minutes, 3, 24, 48 hours after the injection of ProCA32-CXCR4 by tail vein, and before the injection.
Flow cytometry showed differential expression of CXCR4 (percentage): 11.85% of 92.1, 30.7% of M20-07-070, 60.95%% of OMM3, 61.85 % of Mel 290 and 91.0% of M20-09-196.The intraocular melanomas and their hepatic metastases expressed CXCR4 in all strains of mice tested. There were more hepatic metastasis in the mice inoculated by M20-09-196 (a cell line with a high level of CXCR4, 34.33±11.30) than the other cell lines tested (P=0.01). MRI images showed hyper-intensity in hepatic metastases using the T1 weighted spin echo sequence with ProCA32-CXCR4 in vivo, comparing to homogeneity of intensity in liver under pre-scan
All mouse intraocular melanoma models and their hepatic metastases in this study expressed CXCR4, regardless of BAP1 status, host immune status or the level of CXCR4 expression in vitro. While the number of hepatic metastasis is positively correlated with the level of CXCR4 in vitro. MRI with a noval designed CXCR4-targeted contrast agent confirmed overexpression of CXCR4 in hepatic metastases and is capable to detect hepatic metastases in small size. MRI with the noval designed targeted contrast agent might provide the guide to select therapeutic agents.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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