In the present study, we investigated the effect of the
RANTES-mediated interaction between gastric
carcinoma cell lines and peripheral blood mononuclear cells (PBMCs) in
tumor progression.
RANTES production in PBMCs stimulated by highly metastatic
cancer cell line-conditioned supernatants was higher than in those stimulated by a less metastatic
gastric cancer cell line-conditioned supernatant.
RANTES receptors were expressed in PBMCs, but not in those
cancer cell lines; therefore it was suggested that
RANTES might affect PBMCs but not
cancer cells.
Matrix metalloproteinase (MMP)-9 expression in PBMCs was examined. Similar to
RANTES production, MMP-9 expression in PBMCs stimulated by highly metastatic cell line-conditioned supernatants was higher than in that stimulated by a less metastatic cell line-conditioned supernatant. Invasion assays of
gastric cancer cell lines were performed.
Cancer cells cultured with PBMCs invaded into
Matrigel more frequently than those without PBMCs. This invasive activity was highly inhibited by an anti-
RANTES antibody. These results suggest that
tumor cells can acquire the potential for invasion by cooperating with PBMCs and
RANTES plays an important role in the interplay between
tumor cells and PBMCs. It is thus thought that
RANTES might be a candidate molecular target in the therapeutic strategy for
gastric cancers.