Decreased fucose incorporation in cell surface carbohydrates is associated with inhibition of invasion

Abstract

Invasion of malignant MO4 cells into embryonic chick heart fragments in an organ culture assay was arrested for at least 7 days when the temperature was lowered to 28 degrees C. Prolonged culturing of MO4 cells at 28 degrees C on tissue culture substrates showed no recuperation of fucose incorporation into cell surface glycopeptides. However, invasion was restored after 10 days of organ culture in confrontation with chick heart tissue at 28 degrees C. A histoautoradiographic study showed that the regained capability to invade was accompanied by an increase in fucose labeling of the MO4 cells in the invading areas. At 28 degrees C the incorporation of [3H]fucose into total cell protein was drastically reduced, whereas [3H]leucine incorporation as a measure for protein synthesis was less affected. Cell surface glycopeptides, metabolically labeled with either fucose or glucosamine at 28 degrees C, showed a time-dependent decrease in the incorporation of fucose but not of glucosamine and no changes in overall size distribution. Low temperature did not reduce fucosyltransferase activity but the relative accumulation of fucose-1-P suggested inhibited conversion towards GDP-fucose. Moreover, mouse L cells which were incapable of invading chick heart tissue appeared also deficient in fucose incorporation, owing to low levels of fucosyltransferase activity. According to the results, fucosylation of surface carbohydrates may be required for invasive capacity and restored in MO4 cells invading at 28 degrees C by metabolic cooperation with the host tissue.

Antimetabolite-induced increases in the invasive capacity of murine leukaemia L1210 cells

“…Cell surface fucosylation has been demonstrated to play an important role in the cell-cell interactions involved in tumour invasion, and, more recently, in leucocyte extravasation [8,10,12,13,17,31]. When we compare the previously determined changes in monosaccharide incorporation [7] with the now established changes in invasive capacity there is a striking similarity.…”

Altered glycosylation in Madin-Darby canine kidney (MDCK) cells after transformation by murine sarcoma virus

“…The role of fucose in invasion was demonstrated by autoradiography in confronting cultures: resumption of MO4 cell invasion after 10 days of incubation at 28°C was correlated with local recovery of fucose incorporation in the invading MO4 cells [6]. Similarly, fucosyltransferase-deficient L929 cells failed to invade embryonic chick heart fragments in contrast with the corrected L929 x GRSL cells [3].…”

Homotypic Aggregation and Terminal Glycosylation of Cells from Dissociated Human Colorectal Tumor Tissue

“…Elevated fucose serum levels were found in patients with poor prognosis in breast cancer [26]. Recent experiments with murine cells suggest that fucosylation of surface car bohydrates may be required for invasion [11], The func tion of cell-bound fucose for intercellular adhesion of tumor cells still remains unclear. However, our results clearly demonstrate that monitoring of fucose, within serum or biopsy material, could be a promising approach in the search for markers of highly metastasizing tumors.…”

“…This is particularly true for colorectal cancer in which the 5-year survival rate is greater than 60% for patients with localized disease and smaller than 5% for those with disseminated métastasés [1,3], Highly meta static tumor cells possess a variety of specific biochemical properties different from those of normal cells regarding sialylation [4] and fucosylation [5] of cell surface mole cules. Adhesive homotypic interactions are of particular importance for tumor cell detachment from the primary tumor [6] and invasion by tumor cells or the surrounding tissue [7] as well as for the survival of tumor cells during dissemination within the circulatory system [8], We have found that cells obtained by mechanical and enzymatic dissociation of colorectal tumor tissue aggregate very rap idly [9], In this paper homotypic cell aggregation of colon tumor tissue of a number of patients was screened by means of a new aggregation assay [10], Due to the great significance of membrane-bound carbohydrate for adhe sive interactions as well as for invasion and metastasis [4,[11][12][13][14], sialic acid bound to the surface of viable tumor cells and total fucose were determined in parallel experi ments by highly sensitive fluorometric assays. Data ob tained were compared with histological grading and stag ing of the tumors [15].…”