Matrix metalloproteinase digestion of aggrecan in human cartilage tumours

M. Toriyama, Andrew Rosenberg, H. J. Mankin, T. Fondren, B. V. Treadwell, C. A. Towle

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues.

Original languageEnglish
Pages (from-to)1969-1973
Number of pages5
JournalEuropean Journal of Cancer
Volume34
Issue number12
DOIs
StatePublished - Nov 1 1998
Externally publishedYes

Fingerprint

Aggrecans
Matrix Metalloproteinases
Cartilage
Chondrosarcoma
Digestion
Osteochondroma
Extracellular Matrix
Neoplasms
Hyalin
Articular Cartilage
Proteoglycans
Chondrocytes
Western Blotting
Bone and Bones
Antibodies

Keywords

  • Aggrecan
  • Cartilage
  • Chondrosarcoma
  • Metalloproteinase
  • Tumour

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Toriyama, M., Rosenberg, A., Mankin, H. J., Fondren, T., Treadwell, B. V., & Towle, C. A. (1998). Matrix metalloproteinase digestion of aggrecan in human cartilage tumours. European Journal of Cancer, 34(12), 1969-1973. https://doi.org/10.1016/S0959-8049(98)00239-1

Matrix metalloproteinase digestion of aggrecan in human cartilage tumours. / Toriyama, M.; Rosenberg, Andrew; Mankin, H. J.; Fondren, T.; Treadwell, B. V.; Towle, C. A.

In: European Journal of Cancer, Vol. 34, No. 12, 01.11.1998, p. 1969-1973.

Research output: Contribution to journalArticle

Toriyama, M, Rosenberg, A, Mankin, HJ, Fondren, T, Treadwell, BV & Towle, CA 1998, 'Matrix metalloproteinase digestion of aggrecan in human cartilage tumours', European Journal of Cancer, vol. 34, no. 12, pp. 1969-1973. https://doi.org/10.1016/S0959-8049(98)00239-1
Toriyama, M. ; Rosenberg, Andrew ; Mankin, H. J. ; Fondren, T. ; Treadwell, B. V. ; Towle, C. A. / Matrix metalloproteinase digestion of aggrecan in human cartilage tumours. In: European Journal of Cancer. 1998 ; Vol. 34, No. 12. pp. 1969-1973.
@article{46c38312dade454d97591d059a63fe15,
title = "Matrix metalloproteinase digestion of aggrecan in human cartilage tumours",
abstract = "Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues.",
keywords = "Aggrecan, Cartilage, Chondrosarcoma, Metalloproteinase, Tumour",
author = "M. Toriyama and Andrew Rosenberg and Mankin, {H. J.} and T. Fondren and Treadwell, {B. V.} and Towle, {C. A.}",
year = "1998",
month = "11",
day = "1",
doi = "10.1016/S0959-8049(98)00239-1",
language = "English",
volume = "34",
pages = "1969--1973",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Matrix metalloproteinase digestion of aggrecan in human cartilage tumours

AU - Toriyama, M.

AU - Rosenberg, Andrew

AU - Mankin, H. J.

AU - Fondren, T.

AU - Treadwell, B. V.

AU - Towle, C. A.

PY - 1998/11/1

Y1 - 1998/11/1

N2 - Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues.

AB - Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues.

KW - Aggrecan

KW - Cartilage

KW - Chondrosarcoma

KW - Metalloproteinase

KW - Tumour

UR - http://www.scopus.com/inward/record.url?scp=0032213519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032213519&partnerID=8YFLogxK

U2 - 10.1016/S0959-8049(98)00239-1

DO - 10.1016/S0959-8049(98)00239-1

M3 - Article

C2 - 10023324

AN - SCOPUS:0032213519

VL - 34

SP - 1969

EP - 1973

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 12

ER -