This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Miletti-González, K. E. Articles by Rodríguez-Rodríguez, L. Search for Related Content PubMed PubMed Citation Articles by Miletti-González, K. E. Articles by Rodríguez-Rodríguez, L.

The CD44 Receptor Interacts with P-Glycoprotein to Promote Cell Migration and Invasion in Cancer

¹ Departments of Obstetrics and Gynecology and Reproductive Sciences, Divisions of ² Gynecologic Oncology, ³ Pharmacology, ⁴ Medicine, and ⁵ Biometrics, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick, New Jersey

Requests for reprints: Lorna Rodríguez-Rodríguez, Department of Obstetrics and Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick, NJ 08901. Phone: 732-235-8521; Fax: 732-235-9831; E-mail: rodriglo{at}umdnj.edu.

Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of morbidity and mortality from cancer. For more than two decades, these two important but not clearly related aspects in the biology of cancer have been extensively studied. Specifically, P-glycoprotein and CD44 have been characterized and are known to be determinants of multidrug resistance (MDR) and metastases. Despite this body of knowledge, few reports have linked the two phenotypes and only recently have there been reasons to suspect a direct connection. In this report, we show that a novel physical and genetic interaction between CD44s and P-glycoprotein is in part responsible for the correlation between MDR and invasive potential in cancer cells. P-glycoprotein–specific substrates that interfere with its function reduced in vitro invasion, migration, and the physical colocalization of CD44s and P-glycoprotein. CD44 expression in sensitive cells promoted the expression of P-glycoprotein and the MDR phenotype. RNA interference of MDR1 inhibited the rate of cell migration. These data indicate that there is a close interaction between CD44 and P-glycoprotein that results in the concurrent expression and modulation of two malignant phenotypes, invasion and MDR.

This article has been cited by other articles:

				L. Y. W. Bourguignon, K. Peyrollier, W. Xia, and E. Gilad Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells J. Biol. Chem., June 20, 2008; 283(25): 17635 - 17651. [Abstract] [Full Text] [PDF]

				P. Zhang, D. W. Chan, Y. Zhu, J. J. Li, I. O.-L. Ng, D. Wan, and J. Gu Identification of Carboxypeptidase of Glutamate Like-B as a Candidate Suppressor in Cell Growth and Metastasis in Human Hepatocellular Carcinoma. Clin. Cancer Res., November 15, 2006; 12(22): 6617 - 6625. [Abstract] [Full Text] [PDF]

				C Massard, E Deutsch, and J-C Soria Tumour stem cell-targeted treatment: elimination or differentiation Ann. Onc., November 1, 2006; 17(11): 1620 - 1624. [Abstract] [Full Text] [PDF]

				N. Muthukumaran, K. E. Miletti-Gonzalez, A. K. Ravindranath, and L. Rodriguez-Rodriguez Tumor Necrosis Factor-{alpha} Differentially Modulates CD44 Expression in Ovarian Cancer Cells Mol. Cancer Res., August 1, 2006; 4(8): 511 - 520. [Abstract] [Full Text] [PDF]