IN-VIVO INHIBITION OF CD44 LIMITS INTRAABDOMINAL SPREAD OF A HUMAN OVARIAN-CANCER XENOGRAFT IN NUDE-MICE - A NOVEL ROLE FOR CD44 IN THE PROCESS OF PERITONEAL IMPLANTATION

Ovarian cancer cells frequently metastasize by implanting onto the per itoneal mesothelial lining of the abdominal cavity. Data obtained from in vitro adhesion studies have suggested a possible role for the CD44 molecule in this process. The purpose of the present study was to det ermine the in vivo role of CD44 in ovarian cancer metastasis by using a nude mouse xenograft model of peritoneal implantation. Three groups of 10 athymic female nude mice each received an i.p. inoculum of 10 x 10(6) cells from a CD44-positive human ovarian cancer cell line (36M2) in the presence of either anti-D144 antibody (Ab; nonreactive IgG1), anti-DP3 Ab (reactive IgG1 Ab that does not inhibit in vitro binding), or neutralizing anti-CD44 Ab (IgG1), The number of peritoneal and dia phragmatic implants at 5 weeks for anti-D144 and anti-DF3-treated grou ps was 103 +/- 17 and 120 +/- 20, respectively (mean +/- SE; P > 0.2), In contrast, animals treated with anti-CD44 Ab experienced a signific ant reduction in the number of tumor implants (35 +/- 4; P < 0.002). A nti-CD44 Ab was not inhibitory to the growth of 36M2 cells in vitro an d did not inhibit s.c. tumor growth in vivo, suggesting that the obser ved effect was related to inhibition of peritoneal implantation. These data suggest that the CD44 molecule plays an important in vivo role i n ovarian cancer cell implantation and that strategies to inhibit CD44 function may represent a novel approach to limiting the intra-abdomin al spread of this highly lethal tumor.