title: Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells.
abstract: The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis.
authors: From the Departments of Pharmacology.
authors: Jeremy K
authors: JK
authors: Haakenson
authors: the Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and.
authors: Andrei V
authors: AV
authors: Khokhlatchev
authors: the Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and.
authors: Younhee J
authors: YJ
authors: Choi
authors: From the Departments of Pharmacology.
authors: Samuel S
authors: SS
authors: Linton
authors: the Department of Bioengineering, Pennsylvania State University, State College, Pennsylvania 16801.
authors: Pu
authors: P
authors: Zhang
authors: the Department of Bioengineering, Pennsylvania State University, State College, Pennsylvania 16801.
authors: Peter M
authors: PM
authors: Zaki
authors: the Department of Bioengineering, Pennsylvania State University, State College, Pennsylvania 16801.
authors: Changliang
authors: C
authors: Fu
authors: Comparative Medicine.
authors: Timothy K
authors: TK
authors: Cooper
authors: Medicine, and.
authors: Andrea
authors: A
authors: Manni
authors: Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033.
authors: Junjia
authors: J
authors: Zhu
authors: the Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and.
authors: Todd E
authors: TE
authors: Fox
authors: the Department of Bioengineering, Pennsylvania State University, State College, Pennsylvania 16801.
authors: Cheng
authors: C
authors: Dong
authors: From the Departments of Pharmacology, the Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and mkester@virginia.edu.
authors: Mark
authors: M
authors: Kester
mesh_terms: D023102:Anoikis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008081:Liposomes; D008247:Lysosomes / Q000378:metabolism*; D021381:Protein Transport; D059748:Proteolysis
chemical_list: C497483:CD44 protein, human; D002518:Ceramides; D018960:Hyaluronan Receptors; D008081:Liposomes
keywords: Anoikis; Breast Cancer; CD44; Carcinoma; Ceramide; Extravasation; Metastasis