The structure of human chondrosarcoma proteoglycans

J. A BUCKWALTER

doi:10.2106/00004623-198365070-00011

To analyze the structure and dimensions of human chondrosarcoma proteoglycans, proteoglycan subunits and aggregates from eight human chondrosarcomas were examined by electron microscopy. The tumors, identified as malignant neoplasms of cartilage by their clinical presentation and their radiographic and histological appearance, were graded as follows: Grade-I hyaline (one), Grade-II hyaline (five), Grade-II myxoid (one), and Grade-III myxoid (one). Proteoglycans synthesized by chondrosarcoma chondrocytes had the same basic structure as proteoglycans synthesized by normal chondrocytes. The chondrosarcoma proteoglycan subunits consisted of a central core filament representing the core protein, with multiple projecting side-chains consisting primarily of chondroitin sulphate. The core filament had two distinct segments: a thin segment with few if any side-chains and a thick segment with multiple side-chains. Chondrosarcoma proteoglycan aggregates consisted of a single unbranched central filament, representing hyaluronic acid, with multiple attached subunits. Although they had the same basic structure as hyaline-cartilage proteoglycans, chondrosarcoma proteoglycans differed in their dimensions. The chondroitin sulphate chains of chondrosarcoma subunits had a significantly greater average length than those of normal bovine hyaline-cartilage subunits, and the mean length of the subunit core filaments was shorter than that found in normal cartilage. Chondrosarcoma proteoglycan aggregates were smaller than aggregates from normal hyaline cartilage. They had shorter hyaluronic-acid filaments and their subunits were fewer, more widely spaced, and shorter. The chondroitin sulphate chain length of chondrosarcoma subunits may indicate that some malignant chondrocytes have a genetically determined ability to synthesize longer chains of chondroitin sulphate. The shorter subunit core filaments in chondrosarcoma may be due to a difference in protein synthesis, or perhaps to degradation of the core proteins in the matrix. Wider spacing between chondrosarcoma subunits on aggregates may reflect degradation but also may indicate a relative excess of hyaluronic acid, an abnormality in the synthesis of aggregate components, or inhibition of aggregate formation in the chondrosarcoma matrix. Synthesis of an abundant cartilaginous matrix containing a high concentration of proteoglycans distinguishes chondrosarcomas from many other malignant tumors and may contribute significantly to their growth. Cartilage tumors can present difficult clinical problems because they vary greatly in their natural history, histological appearance, and malignancy. In addition, their histological appearance does not always correlate directly with their behavior, making it difficult to reliably identify benign and malignant cartilage neoplasms. This study indicates that although the dimensions of chondrosarcoma proteoglycans vary considerably among tumors, patterns of differences exist between chondrosarcoma matrix proteoglycans and proteoglycans from normal hyaline cartilage. Future investigation of these differences may advance understanding of the synthetic and degradative processes taking place within chondrosarcomas, providing insight into the behavior of these tumors and clarifying the features that characterize malignant neoplasms of cartilage.

The structure of human chondrosarcoma proteoglycans

View Online

Abstract

Details

Metrics