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Originally published online as doi:10.2353/ajpath.2007.070535 on November 8, 2007

Published online before print November 8, 2007
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(American Journal of Pathology. 2007;171:2033-2039.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070535

In Vivo Evidence for the Role of CD44s in Promoting Breast Cancer Metastasis to the Liver

Allal Ouhtit*, Zakaria Y. Abd Elmageed*, Mohamed E. Abdraboh*, Tong F. Lioe{dagger} and Madhwa H.G. Raj{ddagger}

From the Departments of Pathology and Genetics* and Obstetrics and Gynecology,{ddagger} Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana; and the Department of Histopathology,{dagger} Belfast City Hospital, Belfast, United Kingdom

The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including breast carcinomas. CD44 functions as a bioactive signaling transmitter. Although a number of studies have implicated CD44 in breast tumor invasion, the evidence is still circumstantial. We have developed a tetracycline-regulated CD44s (standard form) system in the weakly metastatic breast cancer cell MCF7, which exhibits low endogenous expression of CD44 and generated a new cell line, MCF7F-B5. Induction of CD44s alone affected the growth characteristics of MCF7F-B5 cells by increasing their abilities to proliferate, migrate, and invade in vitro. In addition, we have identified and validated cortactin as a novel transcriptional target of hyaluronan/CD44s signaling in underpinning breast tumor invasion. To test these observations in vivo, we developed a doxycycline (DOX)-regulated CD44s breast cancer xenograft model. Induction of CD44s did not affect the growth rate or local invasion of the primary tumor. However, although no mice from the +DOX group developed metastasis, 8 of 11 mice from the –DOX group developed secondary tumors to the liver only. Interestingly, metastatic breast tumors expressed high levels of CD44. This study provides in vivo evidence for the role of the standard form of CD44 in promoting breast tumor invasion and metastasis to the liver.




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