QUANTITATIVE COMPARISON OF XENOTRANSPLANTATION OF A HUMAN SOFT-TISSUESARCOMA INTO THE SUBCUTANEOUS TISSUE OF NORMAL, POSTINCISION, AND POSTINCISION PLUS INDOMETHACIN-TREATED NUDE-MICE

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and ( 2) Indomethacin may reduce the xenotransplantability of this human tum or in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be ex pected to induce a tumor in 50% of the recipients). After an incisiona l wound (1.0-1.2 cm long) was made on the right leg of each experiment al mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another gr oup tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 c onsecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD(50)s of surgically wounded groups were 3.5-10.7 times lower than that of the control grou ps. Significantly lower TD50 values were found in groups of cells inoc ulated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice t hat received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that th e surgical wound can enhance the xenotransplantability of HSTS26T in n ude mice. Indomethacin can decrease this enhancing effect level simila r to that in no-wound controls and may prevent tumor recurrence in a s urgical wound. (C) 1995 Wiley-Liss, Inc.