Chondroitin sulfate A regulates fibrosarcoma cell adhesion, motility and migration through JNK and tyrosine kinase signaling pathways.
Fibrosarcoma is an uncommon soft tissue tumor with a complex cell microenvironment, particularly rich in glycosaminoglycans/proteoglycans (GAGs/PGs). Chondroitin sulfate proteoglycans (CSPGs) participate in the modulation of various cellular functions, including adhesion and migration. The role of chondroitin sulfate (CS) chains on adhesion, chemotaxis and migration of poorly differentiated fibrosarcoma B6FS cell was studied, utilizing exogenous CS treatment and chondroitinase digestions as well as specific modulators of CS synthesis. Cleavage of cell-associated CS chains and specific inhibition of endogenous CS production severely impaired these fibrosarcoma cell functions. These results show that the reduction of endogenous CSPG expression as well as cleavage of the CS chain inhibited fibrosarcoma cell motility, migration and adhesion. Treatment with free CS chains enhanced cell chemotaxis and migration, whereas adhesion was inhibited. CS chains were found to upregulate cell motility through the MAPK pathway, specifically through JNK, whereas CS-induced migration was found to require tyrosine kinase dependent pathways. This study suggests a new role of CS on tumor cell adhesion, chemotaxis and migration.
Department of Histology, Division of Morphology, School of Medicine, University of Crete, Heraklion, Greece.
Eleni
E
Fthenou
Fang
F
Zong
Alexandros
A
Zafiropoulos
Katalin
K
Dobra
Anders
A
Hjerpe
George N
GN
Tzanakakis
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing
D000970:Antineoplastic Agents; D002809:Chondroitin Sulfates; D011505:Protein-Tyrosine Kinases; D048670:MAP Kinase Kinase 4