RGD-containing peptides inhibit experimental peritoneal seeding of human ovarian cancer cells

A synthetic peptide containing the RGD (Arg-Gly-Asp) sequence is known to inhibit the attachment between cells and the extracellular matrix (ECM) in vitro, and also inhibit experimental pulmonary metastasis of murine melanoma cells in vivo. Prevention of peritoneal seeding by RGD-containing peptides has never previously been discussed. In this study, the inhibition of peritoneal seeding by RGD-containing peptides is examined, using the in vivo experimental peritoneal seeding model with human ovarian cancer cells (JHOC-1). Intraperitoneal (i.p.) inoculation of nude mice with JHOC-1 cells soon resulted in peritoneal seeding in all of the mice. Most of them expired within 4 to 80 weeks, and none survived for as long as 10 weeks. GRGDS (Gly-Arg-Gly-Asp-Ser) sequenced synthetic peptides were administered by i.p. injection after tumor cell inoculation following some regimens, and the changes in body weight and the periods of survival of the peptides-treated and untreated mice were observed. Intraperitoneal administration of 2mg/mouse of GRGDS peptides (every 8 hours, for 4 days, beginning just after tumor cell inoculation) significantly prolonged the survival periods of the tumor implanted mice. In this study, RGD-containing peptides were found to be able to prevent in vivo experimental peritoneal seeding by continual i.p. administration. This might indicate that RGD and integrins plays a critical role in peritoneal seeding as well as in hematogeneous metastasis.