Effect of modulation of claudin-1 expression on tumor xenograft and liver metastasis in vivo. (A) Flank tumor xenografts after subcutaneous injection (n = 5 mice per group) were monitored for SW480^control or 2 individual SW480^claudin-1 clones in nude mice (*P < 0.005 and P = 0.063 for each clone compared with the control group). Conversely, cells expressing either SW620^control or 2 individual SW620^siRNA clones in nude mice were used (P = 0.27 and P = 0.26). The P value was determined using unpaired Student’s t test. (B–G) Liver metastasis. Representative metastatic tumors in livers from SW480^control (B) and SW480^claudin-1 cells (C–E) from experiments on nude mice, with corresponding H&E sections indicating intrahepatic tumors (F and G), are shown. (F) Microscopic examination of the liver tumors confirmed that they represented metastases. (G) Intrahepatic vascular spread was noted. (H–K) SW620 parental or SW620^control cells or 3 individual SW620^siRNA clones were injected in nude mice. Seven weeks after inoculation, metastatic tumors were detected in the livers of nude mice by microPET (H and I) and upon necroscopy (J and K). MicroPET imaging was used to screen for nonpalpable lesions in the liver, using 100–150 μCi of ¹⁸F-deoxyglucose (¹⁸FDG) injected i.p to detect metabolically active foci in the abdomen. The arrows point to the metastatic nodules in the liver. The P value was determined using 2-sided test of proportion.