This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strobel, T. Articles by Cannistra, S. A. Search for Related Content PubMed PubMed Citation Articles by Strobel, T. Articles by Cannistra, S. A.

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 Implantation¹

Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

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 10⁶ 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.

¹ S. A. C. is supported in part by Public Health Service Grant CA 60670.

² To whom requests for reprints should be addressed, at Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: (617) 632-3976; Fax: (617) 632-5148; E-mail: Stephen_Cannistra@dfci.harvard.edu.

Received 11/ 6/96. Accepted 2/20/97.

This article has been cited by other articles:

				Y. Ning, T. Buranda, and L. G. Hudson Activated Epidermal Growth Factor Receptor Induces Integrin {alpha}2 Internalization via Caveolae/Raft-dependent Endocytic Pathway J. Biol. Chem., March 2, 2007; 282(9): 6380 - 6387. [Abstract] [Full Text] [PDF]

				E. E Hanekamp, L. M Kuhne, J A. Grootegoed, C. W Burger, and L. J Blok Progesterone receptor A and B expression and progestagen treatment in growth and spread of endometrial cancer cells in nude mice Endocr. Relat. Cancer, December 1, 2004; 11(4): 831 - 841. [Abstract] [Full Text] [PDF]

				S. Sillanpaa, M. A. Anttila, K. Voutilainen, R. H. Tammi, M. I. Tammi, S. V. Saarikoski, and V.-M. Kosma CD44 Expression Indicates Favorable Prognosis in Epithelial Ovarian Cancer Clin. Cancer Res., November 1, 2003; 9(14): 5318 - 5324. [Abstract] [Full Text] [PDF]

				R. C. Casey, K. M. Burleson, K. M. Skubitz, S. E. Pambuccian, T. R. Oegema Jr., L. E. Ruff, and A. P. N. Skubitz {beta}1-Integrins Regulate the Formation and Adhesion of Ovarian Carcinoma Multicellular Spheroids Am. J. Pathol., December 1, 2001; 159(6): 2071 - 2080. [Abstract] [Full Text] [PDF]

				R. M. Peterson, Q. Yu, I. Stamenkovic, and B. P. Toole Perturbation of Hyaluronan Interactions by Soluble CD44 Inhibits Growth of Murine Mammary Carcinoma Cells in Ascites Am. J. Pathol., June 1, 2000; 156(6): 2159 - 2167. [Abstract] [Full Text] [PDF]

				M. A. Anttila, R. H. Tammi, M. I. Tammi, K. J. Syrjänen, S. V. Saarikoski, and V.-M. Kosma High Levels of Stromal Hyaluronan Predict Poor Disease Outcome in Epithelial Ovarian Cancer Cancer Res., January 1, 2000; 60(1): 150 - 155. [Abstract] [Full Text]

				C. J. Li, Y.-Z. Li, A. V. Pinto, and A. B. Pardee Potent inhibition of tumor survival in vivo by beta -lapachone plus taxol: Combining drugs imposes different artificial checkpoints PNAS, November 9, 1999; 96(23): 13369 - 13374. [Abstract] [Full Text] [PDF]

				X.-Y. Zhang, R. Pettengell, N. Nasiri, V. Kalia, A. G. Dalgleish, and D. P. J. Barton Characteristics and Growth Patterns of Human Peritoneal Mesothelial Cells: Comparison Between Advanced Epithelial Ovarian Cancer and Non-Ovarian Cancer Sources Reproductive Sciences, November 1, 1999; 6(6): 333 - 340. [Abstract] [PDF]

				Y.-T. Tai, T. Strobel, D. Kufe, and S. A. Cannistra In Vivo Cytotoxicity of Ovarian Cancer Cells through Tumor-selective Expression of the BAX Gene Cancer Res., May 1, 1999; 59(9): 2121 - 2126. [Abstract] [Full Text] [PDF]

				S. Kayastha, A. N., F. M., S. Piver, J. Mukkamalla, M. Romero-Guittierez, and B. A. Werness Expression of the Hyaluronan Receptor, CD44S, in Epithelial Ovarian Cancer Is an Independent Predictor of Survival Clin. Cancer Res., May 1, 1999; 5(5): 1073 - 1076. [Abstract] [Full Text] [PDF]

				K. Lessan, D. J. Aguiar, T. Oegema, L. Siebenson, and A. P. N. Skubitz CD44 and ß1 Integrin Mediate Ovarian Carcinoma Cell Adhesion to Peritoneal Mesothelial Cells Am. J. Pathol., May 1, 1999; 154(5): 1525 - 1537. [Abstract] [Full Text] [PDF]