Figure 4. In vivo anti-metastasic effects and tumor targeting in mouse cancer models.

(A) The lung metastases model was established as described in methods. At day 7 after tumor cell injection, mice (n=10/group) were treated with three IV injections (every other day) of vehicle (PBS), or MV-m-uPA. Lung metastases progression was assessed by in vivo bioluminescence imaging at days (−3), 1, and 8 after MV-m-uPA treatment. * p=0.0303. (B). Kaplan-Mier analysis of survival of tumor bearing mice treated with vehicle control or MV-m-uPA. ** p=0.0149. (C) Representative pictures of differences in lung metastases progression by in vivo Bioluminescence imaging. I: Mock. II: MV-m-uPA. (D, E, F) Imunocompetent (Balb/c) mice (n = 3 per group) bearing 4T1 tumors received two intravenous injections of either PBS or MV-m-uPA (1.5×10⁶ TCID₅₀). Lung tissues were harvested 3 days later and frozen sections were used for detection of measles virus. (D) Total RNA was extracted from lung tissues for qRT-PCR analysis of MV-N mRNA. Results were expressed as copies of MV-RNA/μg of total RNA in each organ/tissue. (E) Infectious virus recovery from lung tissues after MV-m-uPA administration. Viral titers are displayed as TCID₅₀/ gram of tissue. (F) Representative pictures of syncytia formation induced by lung tissue lysates of MV-m-uPA treated mice (II) vs. Controls (I). Scale bar = 500 μm. (G) Immunofluorescence (I, II) and immunohistochemical (III, IV) staining of MV-N protein in MV-m-uPA treated vs. control metastases bearing mice. Upper panel: control, lower panel: MV-m-uPA. Scale bar = 50 μm.