Inhibition of metastatic potential by fucosidase: an NMR study identifies a cell surface metastasis marker.
NMR spectroscopy is able to detect subtle changes to the surface chemistry of cells. We have previously shown that high-resolution 1H NMR methods can identify tumor cells with the capacity to metastasize, and we now report that the long T2 relaxation value (500-800 ms) observed in metastatic rat mammary adenocarcinoma cells is removed by treatment with fucosidase. Two-dimensional scalar-correlated NMR (COSY) spectra of fucosidase-treated cells show that a cross peak, consistent with scalar coupling between the methyl and methine groups on fucose and usually associated with malignancy and metastatic ability, is absent. Metastases were observed in only two out of ten rats injected subcutaneously with enzyme-treated cells compared to eight out of ten with untreated cells. NMR studies on isolated cellular lipids identified the long T2 relaxation value only in the ganglioside fraction. This fraction accounts for 51% of the total 14C-labelled fucose incorporated into the cells. We propose that fucogangliosides are an indicator of metastatic potential in rats. The observation that a cell surface metastasis marker has an NMR signal with a characteristically long relaxation value has important consequences for the future use of magnetic resonance imaging and spectroscopy in the cancer clinic.
Wright
L C
LC
Ludwig Institute for Cancer Research (Sydney Branch), Australia.
May
G L
GL
Gregory
P
P
Dyne
M
M
Holmes
K T
KT
Williams
P G
PG
Mountford
C E
CE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009362:Neoplasm Metastasis; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D005644:alpha-L-Fucosidase / Q000494:pharmacology*
D014408:Biomarkers, Tumor; D005644:alpha-L-Fucosidase