THREE-DIMENSIONAL CHANGES IN LYMPHATIC ARCHITECTURE AROUND VX2 TONGUE CANCER DYNAMIC CHANGES AFTER ADMINISTRATION OF ANTIANGIOGENlC AGENT

Abstract

We examined the three-dimensionalchanges of the lymphatic architecture in therabbit VX2 tongue cancer model afteradministration ofan antiangiogenic agent,TNP-470.TNP-470 at 30 mg/kg was administeredvia the auricular vein to the rabbit four timesevery other day from 3 days after transplantationof the tumor. The tongue and bothsides ofdeep cervical lymph nodes of rabbitwere observed at 10 days after transplantation.Lymph node metastasis was confirmedhistopathologically. Morphological changesofcollecting lymphatic vessels and lymphaticcapillaries were observed, and the number anddiameter of lymphatic vessels within 500 pmaround the tumor were measured using thecombined method with 5'-nucleotidase stainingand three-dimensional reconstruction imaging.Tumor growth and lymph node metastasiswere suppressed by administration of TNP470.In the TNP-treatment group, the meannumber of lymphatic capillaries was significantlyfewer than in the control group.The mean diameter ofcollecting lymphaticvessels was significantly smaller than in thecontrol group.In conclusion, our results suggest thatcancer cell invasion into the lymphatics isprobably decreased by inhibiting not only thegrowth of tumor but also new formation oflymphatic capillaries around the tumor byadministration of TNP-470.