Detection of circulating tumor cells is improved by drug-induced antigen up-regulation: Preclinical and clinical studies

Laura Bonmassar, Emanuela Fossile, Alessandro Scoppola, Grazia Graziani, Salvatore P. Prete, Vincenzo Formica, Daniela Cappelletti, Liana De Vecchis, Anna Cardillo, Francesco Concolino, Stefania D'Atri, Alessandra Balduzzi, Francesco Torino, Patrizia Caporaso, Jack W. Greiner, Enzo Bonmassar, Mario Roselli, Angelo Aquino

Research output: Contribution to journalArticle

Abstract

51Cr-prelabelled colon cancer cells (simulating 'circulating tumor cells', CTCs) were added to human peripheral blood and exposed to staurosporine (ST) to increase carcinoembryonic antigen (CEA) expression. CTCs were captured with immunomagnetic beads coated with Ber-EP4 monoclonal antibody, recognizing the common epithelial antigen present in the majority of cancer cells of epithelial origin, with capture efficiency of more than 80%. Moreover, ST treatment increased CEA expression without compromising Ber-EP4 capture efficiency. In a pilot clinical study on 37 patients, CTCs were captured using Ber-EP4 beads, and recognized by RT-PCR set for CEA or cytokeratin-19 (CK) mRNA detection. The results showed that: (a) the percentage of CEA-positive CTCs (CTC CEA, 54.1%) was lower than that of CK-positive CTCs (CTC CK, 70.3%); (b) in vitro ST treatment converted a significant number of CTC CEA-negative into CTC CEA-positive cases. Therefore, immunomagnetic capture combined with exposure to ST provides a feasible and sensitive technique for the detection of functionally-active CTCs responsive to ST-mediated CEA up-regulation.

Original languageEnglish
Pages (from-to)4721-4730
Number of pages10
JournalAnticancer Research
Volume30
Issue number11
Publication statusPublished - Nov 2010

Fingerprint

Circulating Neoplastic Cells
Carcinoembryonic Antigen
Up-Regulation
Antigens
Staurosporine
Pharmaceutical Preparations
Keratin-19
Clinical Studies
Colonic Neoplasms
Epithelial Cells

Keywords

  • Carcinoembryonic antigen
  • Circulating tumor cells
  • Immunomagnetic isolation
  • RT-PCR analysis
  • Staurosporine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bonmassar, L., Fossile, E., Scoppola, A., Graziani, G., Prete, S. P., Formica, V., ... Aquino, A. (2010). Detection of circulating tumor cells is improved by drug-induced antigen up-regulation: Preclinical and clinical studies. Anticancer Research, 30(11), 4721-4730.

Detection of circulating tumor cells is improved by drug-induced antigen up-regulation : Preclinical and clinical studies. / Bonmassar, Laura; Fossile, Emanuela; Scoppola, Alessandro; Graziani, Grazia; Prete, Salvatore P.; Formica, Vincenzo; Cappelletti, Daniela; De Vecchis, Liana; Cardillo, Anna; Concolino, Francesco; D'Atri, Stefania; Balduzzi, Alessandra; Torino, Francesco; Caporaso, Patrizia; Greiner, Jack W.; Bonmassar, Enzo; Roselli, Mario; Aquino, Angelo.

In: Anticancer Research, Vol. 30, No. 11, 11.2010, p. 4721-4730.

Research output: Contribution to journalArticle

Bonmassar, L, Fossile, E, Scoppola, A, Graziani, G, Prete, SP, Formica, V, Cappelletti, D, De Vecchis, L, Cardillo, A, Concolino, F, D'Atri, S, Balduzzi, A, Torino, F, Caporaso, P, Greiner, JW, Bonmassar, E, Roselli, M & Aquino, A 2010, 'Detection of circulating tumor cells is improved by drug-induced antigen up-regulation: Preclinical and clinical studies', Anticancer Research, vol. 30, no. 11, pp. 4721-4730.
Bonmassar, Laura ; Fossile, Emanuela ; Scoppola, Alessandro ; Graziani, Grazia ; Prete, Salvatore P. ; Formica, Vincenzo ; Cappelletti, Daniela ; De Vecchis, Liana ; Cardillo, Anna ; Concolino, Francesco ; D'Atri, Stefania ; Balduzzi, Alessandra ; Torino, Francesco ; Caporaso, Patrizia ; Greiner, Jack W. ; Bonmassar, Enzo ; Roselli, Mario ; Aquino, Angelo. / Detection of circulating tumor cells is improved by drug-induced antigen up-regulation : Preclinical and clinical studies. In: Anticancer Research. 2010 ; Vol. 30, No. 11. pp. 4721-4730.
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abstract = "51Cr-prelabelled colon cancer cells (simulating 'circulating tumor cells', CTCs) were added to human peripheral blood and exposed to staurosporine (ST) to increase carcinoembryonic antigen (CEA) expression. CTCs were captured with immunomagnetic beads coated with Ber-EP4 monoclonal antibody, recognizing the common epithelial antigen present in the majority of cancer cells of epithelial origin, with capture efficiency of more than 80{\%}. Moreover, ST treatment increased CEA expression without compromising Ber-EP4 capture efficiency. In a pilot clinical study on 37 patients, CTCs were captured using Ber-EP4 beads, and recognized by RT-PCR set for CEA or cytokeratin-19 (CK) mRNA detection. The results showed that: (a) the percentage of CEA-positive CTCs (CTC CEA, 54.1{\%}) was lower than that of CK-positive CTCs (CTC CK, 70.3{\%}); (b) in vitro ST treatment converted a significant number of CTC CEA-negative into CTC CEA-positive cases. Therefore, immunomagnetic capture combined with exposure to ST provides a feasible and sensitive technique for the detection of functionally-active CTCs responsive to ST-mediated CEA up-regulation.",
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AU - Graziani, Grazia

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AU - Torino, Francesco

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AU - Greiner, Jack W.

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AU - Roselli, Mario

AU - Aquino, Angelo

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