Lentivirus-Based DsRed-2-Transfected Pancreatic Cancer Cells for Deep In Vivo Imaging of Metastatic Disease

Pancreatic cancer is one of the most aggressive human malignancies. One of the leading causes of pancreatic cancer death is metastasis. In this report, we developed in vitro, a stable high-expression red fluorescent protein (RFP) transductant of the pancreatic cancer cells with a lentiviral expression vector containing the DsRed-2 RFP gene. These fluorescent pancreatic cancer cells were used to establish an orthotopic metastatic model and an experimental angiogenesis metastatic model of pancreatic cancer in nude mice. The high-level expression of RFP enables the imaging of distant micrometastases in their target organs. RFP expression did not interfere with the biological properties of the transformed cells compared to the parental cell line. We also demonstrated that lentiviral-transduced pancreatic cancer cells maintained stable high-level RFP expression during their growth in vitro and in vivo. The fluorescence was sufficient to noninvasively image tumor growth and metastasis, even in deep tissue such as the lung. The results indicate the benefit of lentivirus transfection of cancer cells for high expression of RFP and for sensitive in vivo imaging of metastatic pancreatic cancer.

Key Words: pancreatic cancer, metastasis, micrometastasis, green fluorescent protein, red fluorescent protein