Abstract 3: Imaging of stromal cells during hepatocellular metastasis formation in the RFP-MUP-uPA mouse

Abstract Major urinary protein-urokinase type plasminogen activator (MUP-uPA) transgenic mice develop liver disease. We have developed the RFP-MUP-uPA mice, by crossing MUP-uPA mice with transgenic mice ubiquitously-expressing RFP. Hepatocyte RFP fluorescence in this model is very strong. In addition, RFP fluorescence of stromal cells is very bright enabling the portal vein and sinusoid structures to be clearly visualized. Huh7 liver cancer cells expressing green fluorescent protein (GFP) were injected in the spleen of MUP-uPA transgenic mice. The vessels of the MUP-uPA liver are filled with Huh7-GFP cells as imaged in live mice 3h after cell injection. Huh7-GFP cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. The Huh7-GFP cells were visualized in the liver with the Olympus FV1000 confocal microscope. In large metastatic liver tumors in RFP-MUP-uPA mice, stroma cells derived from the host animal appeared around and into the edge of Huh7-GFP tumors. In contrast, in small metastatic liver tumors, there were no stromal cells observed. The stromal cells were observed in the spleen primary tumor, as well as kidney and the lung metastasis in addition to the large liver tumors. This model enables imaging the effects of uPA on liver metastasis and stromal recruitment enabling the metastasis to progress. Citation Format: Atsushi Suetsugu, Hisanobu Ogata, Yukihiko Hiroshima, Masashi Momiyama, Yosuke Osawa, Hisataka Moriwaki, Shigetoyo Saji, Michael Karin, Robert M. Hoffman. Imaging of stromal cells during hepatocellular metastasis formation in the RFP-MUP-uPA mouse. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3. doi:10.1158/1538-7445.AM2014-3