Tumour seeding in peritoneal wound sites in relation to growth-factor expression in early granulation tissue

The purpose of these experiments was to identify growth factors produced during the formation of a peritoneal wound in relation to tumour cell seeding and stimulated growth in granulation tissue. Gelfoam(c) gelatin sponge was implanted in the mesenteric fan of nude mice to initiate the granulation process. Human HT29 colon carcinoma cells were inoculated intraperitoneally at various times after sponge implantation and tumour growth in granulation tissue was determined. RNA isolated from granulation tissue was used for polymerase chain reaction analysis of the expression of specific growth factors and receptors [vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta) and lysophosphatic acid (LPA)], and for microarray analysis of differentially expressed genes in early vs. late granulation tissue. Inflammatory cells infiltrated the sponge within 1 day, followed by fibroblasts and the formation of an extracellular matrix. Tumour cell inoculation at 8 h to 3 days after sponge implantation resulted in extensive tumour formation in all cases. Inoculation at 10-28 days resulted in focal tumour growth in only 16-33% of the sponges. Low amounts of VEGF, TGF-beta(1-3), TGF-beta RIII and LPA receptors 1,2 were detected in early granulation tissue, with increased expression from day 10. Microarray analysis identified additional differentially expressed genes that may stimulate tumour take and growth in early granulation tissue.