Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells

A. Aquino, S. P. Prete, F. Guadagni, J. W. Greiner, A. Giuliani, L. Orlando, G. Masci, S. De Santis, E. Bonmassar, G. Graziani

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. Materials and Methods: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis; (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. Results: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. Conclusions: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.

Original languageEnglish
Pages (from-to)3475-3484
Number of pages10
JournalAnticancer Research
Volume20
Issue number5 B
Publication statusPublished - 2000

Fingerprint

Carcinoembryonic Antigen
Fluorouracil
Colonic Neoplasms
Antimetabolites
Antigens
Neoplasms
Tumor Biomarkers
Tumor Cell Line
Northern Blotting
Flow Cytometry
Membrane Proteins
Cytoplasm
Clone Cells
Western Blotting
Cell Membrane

Keywords

  • 5-fluorouracil
  • Carcinoembryonic antigen
  • Colon cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aquino, A., Prete, S. P., Guadagni, F., Greiner, J. W., Giuliani, A., Orlando, L., ... Graziani, G. (2000). Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells. Anticancer Research, 20(5 B), 3475-3484.

Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells. / Aquino, A.; Prete, S. P.; Guadagni, F.; Greiner, J. W.; Giuliani, A.; Orlando, L.; Masci, G.; De Santis, S.; Bonmassar, E.; Graziani, G.

In: Anticancer Research, Vol. 20, No. 5 B, 2000, p. 3475-3484.

Research output: Contribution to journalArticle

Aquino, A, Prete, SP, Guadagni, F, Greiner, JW, Giuliani, A, Orlando, L, Masci, G, De Santis, S, Bonmassar, E & Graziani, G 2000, 'Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells', Anticancer Research, vol. 20, no. 5 B, pp. 3475-3484.
Aquino, A. ; Prete, S. P. ; Guadagni, F. ; Greiner, J. W. ; Giuliani, A. ; Orlando, L. ; Masci, G. ; De Santis, S. ; Bonmassar, E. ; Graziani, G. / Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells. In: Anticancer Research. 2000 ; Vol. 20, No. 5 B. pp. 3475-3484.
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abstract = "Background: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. Materials and Methods: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis; (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. Results: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. Conclusions: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.",
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T1 - Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells

AU - Aquino, A.

AU - Prete, S. P.

AU - Guadagni, F.

AU - Greiner, J. W.

AU - Giuliani, A.

AU - Orlando, L.

AU - Masci, G.

AU - De Santis, S.

AU - Bonmassar, E.

AU - Graziani, G.

PY - 2000

Y1 - 2000

N2 - Background: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. Materials and Methods: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis; (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. Results: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. Conclusions: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.

AB - Background: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. Materials and Methods: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis; (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. Results: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. Conclusions: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.

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