Cartilage aggrecan undergoes significant compositional and structural alterations during laryngeal cancer.
Aggrecan is a key component of cartilage and is responsible for the integrity and function of the tissue. In this study, the content of aggrecan and its structural modifications in adjacent to cancer apparently normal cartilages (AANCs) from various stages of laryngeal squamous cell carcinoma (LSCC) were investigated. Our data demonstrated a stage-related loss of aggregable aggrecan in AANCs, compared to the healthy laryngeal cartilage (HLC), which was excessive in advanced stages of disease. On aggregable aggrecan level, AANCs were characterized by significant compositional and structural modifications, the extent of which was closely related with the stage of LSCC. Four concrete subpopulations of aggregable molecules with particular physicochemical characteristics were identified with a strong tendency to prevail subpopulations of molecules of lower hydrodynamic sizes with increasing LSCC stage. These findings demonstrated that the cleavage of aggregable aggrecan occurred in concrete peptide bonds within the CS-1 and CS-2 attachment domains. These significant alterations were closely associated with the process of cartilage destruction, indicating the crucial role of aggrecan during LSCC.
Skandalis
Spyros S
SS
Laboratory of Biochemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Department of Chemistry, University of Patras, 26500 Patras, Greece.
Theocharis
Achilleas D
AD
Vynios
Demitrios H
DH
Papageorgakopoulou
Nickoletta
N
Hjerpe
Anders
A
Karamanos
Nikos K
NK
Theocharis
Dimitrios A
DA
D000328:Adult; D053674:Aggrecans; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D037181:Lectins, C-Type; D010455:Peptides