Details

Autor(en) / Beteiligte

• Goupille, C.
• Marionneau, S.
• Bureau, V.
• Hallouin, F.
• Meichenin, M.
• Rocher, J.
• Le Pendu, J.

Titel

1,2Fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells

Ist Teil von

• Glycobiology (Oxford), 2000-04, Vol.10 (4), p.375-382

Ort / Verlag

Oxford: Oxford Publishing Limited (England)

Erscheinungsjahr

2000

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H in colon cancer is indicative of poor prognosis. It is accompanied by increase in [alpha]1,2fucosyl-transferase activity, a key enzyme for synthesis of these antigens. Using a model of colon carcinoma, we previously showed that [alpha]1,2fucosylation increases tumorigenicity. We now show that tumorigenicity inversely correlates with the cells' sensitivity to apoptosis. In addition, poorly tumorigenic REG cells independently transfected with three different [alpha]1,2fucosyltransferase cDNAs, the human FUT1, the rat FTA and FTB were more resistant than control cells to apoptosis induced in vitro by serum deprivation. Inversely, PRO cells, spontaneously tumorigenic in immunocompetent syngeneic animals and able to synthesize [alpha]1,2fucosylated glycans, became more sensitive to apoptosis after transfection with a fragment of the FTA cDNA in the antisense orientation. Expression of [alpha]1,2fucosyl-transferase in poorly tumorigenic REG cells dramatically enhanced their tumorigenicity in syngeneic rats. However, in immunodeficient animals, both control and [alpha]1,2fuco-syltransferase transfected REG cells were fully tumorigenic and metastatic, indicating that the presence of [alpha]1,2fucosylated antigens allowed REG tumor cells to escape immune control. Taken together, the results show that increased tumorigenicity mediated by [alpha]1,2fucosyl-ation is associated to increased resistance to apoptosis and to escape from immune control.