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. Author manuscript; available in PMC: 2018 Oct 9.
Published in final edited form as: Sci Transl Med. 2018 May 16;10(441):eaap8307. doi: 10.1126/scitranslmed.aap8307

Figure 2: Metarrestin treatment reduces metastasis to the lungs and liver in NOD/IL2 gamma (null) PANC1 mice.

Figure 2:

(A) A panel of pancreatic cancer cell lines derived from either primary pancreatic tumors or metastatic lesions showed a higher PNC prevalence in cells derived from metastasis than from primary tumors (cell line explanations in table S2). (B) PNC prevalence increased in metastatic tissues (red) from NOD/IL2 gamma (null) PANC1 mice over primary tumor tissues (yellow), harvested 8 weeks after implantation. PNC prevalence was determined on frozen tissue sections stained with SH54 antibodies. (C) After six weeks of treatment, metastatic deposits measured by organ/tumor ratio in liver and lungs decreased in mice treated once daily with 25 mg/kg of metarrestin compared to vehicle-treated animals (n=10 mice were randomized to each cohort). (D) Pathology and (E) histological examinations demonstrated that livers and lungs from metarrestin-treated animals have a reduced metastatic burden compared to those treated with vehicle (bar=250 μm; n=4 animals per group analyzed). (F) The primary tumors in treated animals were not changed. (G) Treatment was well tolerated, and there were no significant weight differences between treatment groups across the duration of the experiment. (H) Metarrestin disassembles PNCs in primary pancreatic tumors and metastases of NSG PANC1 mice. PNCs in tumors were visualized via immunofluorescence (PNCs labeled green and marked with arrows, nucleoli labeled pink, DAPI, blue) 12 weeks after inoculation. Images from the primary tumors and liver metastases are shown (scale bar = 5 μm). Vehicle-treated animals showed typical, easily detectable PNCs. PNC prevalence was reduced and remaining PNCs appeared smaller in metarrestin-treated animals (25 mg/kg IP daily for 6 weeks; n=4 animals per group analyzed). (I) Metarrestin effect on PNC prevalence in primary pancreatic tumors and sites of metastasis. PNC prevalence was reduced with metarrestin treatment (25 mg/kg IP daily for 6 weeks) in the primary tumor (pancreas) and in metastatic tumors in the lung, liver, and spleen. * P < 0.05, ** P < 0.01, *** P < 0.001.