In vivo inhibition of CD44 limits intra-abdominal 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 peritoneal 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 determine 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-DF3 Ab (reactive IgG1 Ab that does not inhibit in vitro binding), or neutralizing anti-CD44 Ab (IgG1). The number of peritoneal and diaphragmatic implants at 5 weeks for anti-D144 and anti-DF3-treated groups was 103 +/- 17 and 120 +/- 20, respectively (mean +/- SE; P > 0.2). In contrast, animals treated with anti-CD44 Ab experienced a significant reduction in the number of tumor implants (35 +/- 4; P < 0.002). Anti-CD44 Ab was not inhibitory to the growth of 36M2 cells in vitro and did not inhibit s.c. tumor growth in vivo, suggesting that the observed effect was related to inhibition of peritoneal implantation. These data suggest that the CD44 molecule plays an important in vivo role in ovarian cancer cell implantation and that strategies to inhibit CD44 function may represent a novel approach to limiting the intra-abdominal spread of this highly lethal tumor.
Strobel
T
T
Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Swanson
L
L
Cannistra
S A
SA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D002455:Cell Division; D003964:Diaphragm; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000517:prevention & control / Q000556:secondary*; D012878:Skin Neoplasms / Q000517:prevention & control / Q000556:secondary; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors