METASTATIC PATTERNS OF LUNG-CANCER VISUALIZED LIVE AND IN-PROCESS BY GREEN FLUORESCENCE PROTEIN EXPRESSION

We demonstrate here the visualization of human lung canter metastasis live and in process in nude mice by green fluorescent protein (GFP) ex pression, The human lung adenocarcinoma cell line Anip 973 stably tran sfected with the humanized GFP-S65T cDNA was selected for very bright green fluorescence, GFP-transfected lung cancer cells were initially i noculated subcutaneously in nude mice, Five weeks after transplantatio n, the resulting tumor had reached over 1 cm in diameter and had very bright GFP fluorescence, Fragments of subcutaneous tumor were implante d onto the visceral pleura of the left lung of nude mice by surgical o rthotopic implantation (SOI) of histologically-intact tissue via trans verse thoracotomy, The ipsilateral resulting tumor was highly fluoresc ent due to GFP expression, GFP expression allowed the visualization of the advancing margin of the ipsilateral tumor into the fresh normal l ung tissue, Lymphogenous and direct-seeding metastases in the pulmonar y hilum, cervical lymph nodes, the mediastinum and contralateral pleur al cavity and contralateral lung in the SOI-treated mice were brightly visualized by GFP expression in fresh tissue, GFP-transfected and unt ransfected tumor had similar metastatic characteristics suggesting tha t GFP expression had no effect on metastasis itself, The results with the GFP-transfected tumor cells, combined with the use of SOI, demonst rate a fundamental advance in the visualization and study of lung canc er metastasis in process.