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, Madhwa H G Raj

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2033-2039
Number of pages7
JournalAmerican Journal of Pathology
Volume171
Issue number6
DOIs
Publication statusPublished - Dec 2007

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Breast Neoplasms
Neoplasm Metastasis
Liver
Doxycycline
Cortactin
CD44 Antigens
Neoplasms
MCF-7 Cells
Hyaluronic Acid
Growth
Tetracycline
Heterografts
Cell Line

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Ouhtit, A., Abd Elmageed, Z. Y., Abdraboh, M. E., Lioe, T. F., & Raj, M. H. G. (2007). In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. American Journal of Pathology, 171(6), 2033-2039. https://doi.org/10.2353/ajpath.2007.070535

In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. / Ouhtit, Allal; Abd Elmageed, Zakaria Y.; Abdraboh, Mohamed E.; Lioe, Tong F.; Raj, Madhwa H G.

In: American Journal of Pathology, Vol. 171, No. 6, 12.2007, p. 2033-2039.

Research output: Contribution to journalArticle

Ouhtit, A, Abd Elmageed, ZY, Abdraboh, ME, Lioe, TF & Raj, MHG 2007, 'In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver', American Journal of Pathology, vol. 171, no. 6, pp. 2033-2039. https://doi.org/10.2353/ajpath.2007.070535
Ouhtit, Allal ; Abd Elmageed, Zakaria Y. ; Abdraboh, Mohamed E. ; Lioe, Tong F. ; Raj, Madhwa H G. / In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. In: American Journal of Pathology. 2007 ; Vol. 171, No. 6. pp. 2033-2039.
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