Modulation of membrane phenotype, matrix adhesion and microinvasiveness of metastatic tumour cells by HUdR.
The effect of HUdR, proved to be anti-metastatic in vivo, was studied in vitro on cell proliferation, nucleoside uptake, membrane fluidity, expression of galactosylated glycans and proteoglycans in metastatic HM tumour cells. The observed increase in membrane fluidity and the suppression of nucleoside transport were early events of the HUdR action followed by decrease of galactosylated glycan and HSPG expression. However, these changes did not influence the proliferation capacity of the cells at the concentrations studied. As a consequence of the membrane alterations a reduced adhesiveness and spreading on extracellular matrix components was detected. In addition, the HUdR treated HM cells showed reduced capacity to invade fibroblast monolayers in vitro. Based on these observations, HUdR could be the prototype of new anti-metastatic agents acting at the level of tumour-host interaction.
Timár
J
J
1st Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary.
Pogány
G
G
Balázs
M
M
Szöllösi
J
J
Ladányi
A
A
Oláh
J
J
Timár
F
F
Lapis
K
K
Jeney
A
A
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology; D006001:Glycoconjugates / Q000032:analysis; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D009705:Nucleosides / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans / Q000276:immunology; D014316:Tritium
D000954:Antigens, Surface; D000964:Antimetabolites, Antineoplastic; D006001:Glycoconjugates; D009705:Nucleosides; D011509:Proteoglycans; D014316:Tritium; C064952:5-hexyl-2'-deoxyuridine; D003857:Deoxyuridine