STIMULATION OF TUMOR ANGIOGENESIS BY PROXIMAL WOUNDS - SPATIAL AND TEMPORAL ANALYSIS BY MRI

We show here, using high-resolution magnetic resonance imaging, that i njured tissue provides a favourable milieu for the neovascularization and growth of C6 glioma spheroids, implanted subcutaneously in nude mi ce. Moreover, the presence of micro-tumours in an injured tissue inhib ited the healing process, leaving an open persistent wound. In correla tion with the induced angiogenesis of implanted spheroids in the prese nce of proximal wounds, a shorter lag period was observed for initiati on of tumour growth. This effect was restricted spatially and was obse rved only for wounds within 5 mm from the tumour. In such proximal wou nds, angiogenesis was enhanced in the first days after injury, and ves sel regression, which normally starts 4 days after injury, did not occ ur. Injury causing interference to tumour perfusion promoted tumour va scularization and growth even for more remote incisions, possibly by a ctivating stress-induced angiogenesis. The kinetics of vascularization and growth of these wound-tumour systems sheds light on the clinical observations of increased probability of metastatic recurrence and sti mulated regrowth of residual tumour in the site of surgical interventi on. High-resolution magnetic resonance imaging could detect the aberra nt angiogenic activity of these tumour-wound systems as early as 1 wee k after injury.