The Antimetabolite Tiazofurin (TR) Inhibits Glycoconjugate Biosynthesis and Invasiveness of Tumour Cells

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We investigated the effect of Tiazofurin (TR-2-β-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 μM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of αvβ3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 μM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.

Original languageEnglish
Pages (from-to)152-159
Number of pages8
JournalEuropean Journal of Cancer
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 1996

Fingerprint

tiazofurin
Antimetabolites
Glycoconjugates
Neoplasms
Cell Proliferation
Cell Adhesion
Integrins
Lung
Melanoma
Neoplasm Metastasis
Carcinoma

Keywords

  • 3LL carcinoma
  • Glycoconjugates
  • Human melanoma
  • Integrin
  • Metastasis
  • MMP2
  • Tiazofurin

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

@article{57fb8eb4b8c0415eb9e44b42ca1464d2,
title = "The Antimetabolite Tiazofurin (TR) Inhibits Glycoconjugate Biosynthesis and Invasiveness of Tumour Cells",
abstract = "We investigated the effect of Tiazofurin (TR-2-β-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 μM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of αvβ3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 μM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.",
keywords = "3LL carcinoma, Glycoconjugates, Human melanoma, Integrin, Metastasis, MMP2, Tiazofurin",
author = "J. T{\'i}m{\'a}r and J. T{\'o}v{\'a}ri and G. Pog{\'a}ny and A. Lad{\'a}nyi and S. Paku and E. R{\'a}s{\'o} and J. Bocsi and A. Jeney and K. Lapis",
year = "1996",
month = "1",
doi = "10.1016/0959-8049(95)00544-7",
language = "English",
volume = "32",
pages = "152--159",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - The Antimetabolite Tiazofurin (TR) Inhibits Glycoconjugate Biosynthesis and Invasiveness of Tumour Cells

AU - Tímár, J.

AU - Tóvári, J.

AU - Pogány, G.

AU - Ladányi, A.

AU - Paku, S.

AU - Rásó, E.

AU - Bocsi, J.

AU - Jeney, A.

AU - Lapis, K.

PY - 1996/1

Y1 - 1996/1

N2 - We investigated the effect of Tiazofurin (TR-2-β-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 μM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of αvβ3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 μM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.

AB - We investigated the effect of Tiazofurin (TR-2-β-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 μM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of αvβ3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 μM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.

KW - 3LL carcinoma

KW - Glycoconjugates

KW - Human melanoma

KW - Integrin

KW - Metastasis

KW - MMP2

KW - Tiazofurin

UR - http://www.scopus.com/inward/record.url?scp=0029915380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029915380&partnerID=8YFLogxK

U2 - 10.1016/0959-8049(95)00544-7

DO - 10.1016/0959-8049(95)00544-7

M3 - Article

VL - 32

SP - 152

EP - 159

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 1

ER -