Abstract
The patterns of acidic and neutral glycosphingolipids (GSLs) were examined in a syngeneic tumour system in Balb/c mice consisting of closely related cell lines with different colonisation potentials directed to the murine lungs (in vivo selected highly metastatic sublines of L1-fibrosarcoma cells and their WGA-resistant mutants with low metastatic potential). GSLs were analysed by high-performance thin-layer chromatography and structurally identified by fast atom bombardment mass spectrometry combined with compositional analyses and exo-glycosidase digestion. The results suggest that highly metastatic sublines L1-LM and L1-LM12 derived by in vivo selection from mouse fibrosarcoma cells (cell line L1) exhibit a drastic increase of polar ganglioside expression and a restriction to globo-series GSLs. Contrasting with this the low metastatic mutant cells (L1-LM13WGA) express a reduced portion of acidic GSLs and exhibit a shift to less polar ganglioside components. Total cellular and plasma membrane-integrated GSLs were demonstrated to exhibit largely identical patterns. Concomitant with a significant decrease in LacCer expression a substantial reduction of GM2 and a complete lack of GM3 expression can be assigned to the highly metastatic sublines of L1-cells. On the other hand, the more polar gangliosides GM1a and, to an even greater extent, GD1a (exceeding 70% of total gangliosides) accumulate on L1-LM and their clonal sublines. The shift to acidic GSLs of higher polarity is less pronounced on the low metastatic WGA-resistant mutant cells (L1-LM13WGA) showing a preponderance of GM1a. The portion of GD1a within the fractions of acidic GSLs does not correspond to the cellular activities of CMP-NeuAc/GM1 (alpha 2-3) sialyltransferase measured for high and low metastatic cell variants. Total sialic acid content of the various cell lines differs, but is not associated with the metastatic potential. Gangliosides on L1-cells exhibit a significant substitution of N-glycolyl for N-acetylneuraminic acid (13%) compared to their metastatic sublines and to mutant cells (less than 1%). A conversion of surface exposed GD1a to GM1a on membranes of metastatic cells by in situ treatment with Vibrio cholerae sialidase is associated with a significant reduction of tumour cell colonisation directed to the murine lungs.
Highlights
A similar 'homing' phenomenon in the organotropy of native L1-cells can be postulated for murine lung colonisation
Since cell surface glycoconjugates of this tumour system have not been studied on a sound chemical basis, the present contribution is an attempt to define variations in the glycosphingolipid expression on L 1 -fibrosarcoma sublines colonising the lungs at different rates after i.v. inoculation
Murine tumour cells cultured from lung metastases of Lifibrosarcoma (L1-LM, LI-LM12) and WGA-resistant mutant LILM13 (WGA)-resistant mutant cells (LI-LM13 WGA) were analysed with regard to their GSL patterns by HPTLC prior to and after metabolic radiolabelling with '4C-galactose
Summary
Of high significance for the purpose of this study is the previously published work on metastatic sublines of virally transformed murine 3T3 fibroblasts suggesting that a higher metastatic level into mouse lung is correlated with increased expression of Gg3Cer and GM3 (Yogeeswaran & Stein, 1980)
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