Cell surface CD44-related chondroitin sulfate proteoglycan is required for transforming growth factor-beta-stimulated mouse melanoma cell motility and invasive behavior on type I collagen.
Tumor cell metastasis involves a complex series of events, including the adhesion, migration and invasive behavior of tumor cells on components of the extracellular matrix. Multiple cell surface receptors mediate interactions with the surrounding extracellular matrix and thereby influence cell adhesion, motility and invasion. We have previously described a cell surface CD44-related chondroitin sulfate proteoglycan on highly metastatic melanoma cells. CD44-chondroitin sulfate proteoglycan was shown to be important in melanoma cell motility and invasive behavior on type I collagen matrices. In our current studies, the role of cell surface CD44-chondroitin sulfate proteoglycan in collagen-mediated mouse melanoma cell migration and invasive behavior is further evaluated using transforming growth factor-beta 1. We report that transforming growth factor-beta 1 stimulates the migratory and invasive behavior of mouse melanoma cells on type I collagen. Transforming growth factor-beta 1 stimulated cell surface CD44-chondroitin sulfate proteoglycan synthesis in mouse melanoma cells, specifically through an upregulation of chondroitin sulfate production, while the expression of CD44-chondroitin sulfate proteoglycan core protein was not affected. Furthermore, transforming growth factor-beta 1-mediated enhancement of cell polarity, migration and invasive behavior on type I collagen gels was markedly inhibited in the presence of beta-D-xyloside, an agent that blocks chondroitin sulfate addition to the core protein. Collectively, our findings indicate that mouse melanoma cell surface CD44-chondroitin sulfate proteoglycan is required for transforming growth factor-beta 1-enhanced cell motility and invasion, and that CD44-chondroitin sulfate proteoglycan may play a role in forming and/or maintaining a dominant leading lamella, which is required for efficient locomotion.
Faassen
A E
AE
Department of Laboratory Medicine, University of Minnesota Hospital and Clinics, Minneapolis 55455.
Mooradian
D L
DL
Tranquillo
R T
RT
Dickinson
R B
RB
Letourneau
P C
PC
Oegema
T R
TR
McCarthy
J B
JB
D053674:Aggrecans; D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D003094:Collagen; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006027:Glycosides / Q000494:pharmacology; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011509:Proteoglycans; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C508320:Acan protein, mouse; D053674:Aggrecans; D000951:Antigens, Neoplasm; D011508:Chondroitin Sulfate Proteoglycans; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006027:Glycosides; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D011509:Proteoglycans; D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta; C010807:xylosides; D003094:Collagen