WOUND-INDUCED TUMOR PROGRESSION - A PROBABLE ROLE IN RECURRENCE AFTERTUMOR RESECTION

Objective: To determine the effect of several wound factors on melanom a growth in a mouse model. Design: Cohort analytic study. Setting: Ani mal research facility of Roger Williams Medical Center, Providence, RI . Study Group: Seventeen groups of 5 C57BL/6 mice each. Interventions: A surgical wound was created in 1 hind limb, after which different co ncentrations of B16F10 melanoma cells were injected in adjacent subcut aneous tissue. The nonwounded hind limb in the same mouse served as a control. In this fashion, a critical tumor cell dose was determined th at showed tumor growth in the wounded but not the control hind limb. T umor growth in control hind limbs then was compared with that in the ' 'artificially wounded'' hind limbs, which were co-injected with mouse wound fluid or growth factors. Early (day 1) and late (day 10) wound f luids and tumor growth factor beta (TGF-beta), basic fibroblast growth factor (bFGF), both combined, and interleukin 6 (IL-6) were used. Mai n Outcome Measure: Wound factors increase tumor growth, indicating pot entiation of tumor recurrence at a surgical wound. Results: The critic al tumor cell dose was 103 cells. All growth factors and both wound fl uids showed increased tumor growth over time except IL-6. Hind limbs i njected with early wound fluid showed increased tumor growth over time when compared with those injected with late wound fluid (P<.001), TGF -beta (P<.001), bFGF (P<.001), and IL-6 (P<.001). Combined TGF-beta an d bFGF coinjection resulted in increased tumor growth compared with TG F-beta (P<.001) and bFGF (P<.001), but did not differ significantly fr om early wound fluid (P<.07). Conclusions: The healing wound and its m ediators in wound fluid or purified growth factors significantly enhan ced tumor growth. Combining TGF-beta and bFGF increased tumor growth t o a level closer to wound fluid. The inflammatory response provoked by wound healing mediators may be an important mechanism in tumor growth after ablative surgery.