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Cited by 324

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction

Open access
Contardi, Elisabetta, Palmisano, Giulio L., Tazzari, Pier Luigi, Martelli, Alberto M., Falà, Federica, Fabbi, Marina, Kato, Tomohiro, Lucarelli, Enrico, Donati, Davide, Polito, Letizia, Bolognesi, Andrea, Ricci, Francesca, Salvi, Sandra, Gargaglione, Vittoria, Mantero, Stefano, Alberghini, Marco, Ferrara, Giovanni Battista, Pistillo, Maria Pia·2005·International Journal of Cancer

Abstract

CTLA-4 (CD152) is a cell surface receptor that behaves as a negative regulator of the proliferation and the effector function of T cells. We have previously shown that CTLA-4 is also expressed on neoplastic lymphoid and myeloid cells, and it can be targeted to induce apoptosis. In our study, we have extended our analysis and have discovered that surface expression of CTLA-4 is detectable by flow cytometry on 30 of 34 (88%) cell lines derived from a variety of human malignant solid tumors including carcinoma, melanoma, neuroblastoma, rhabdomyosarcoma and osteosarcoma (but not in primary osteoblast-like cultures). However, by reverse transcriptase-PCR, CTLA-4 expression was detected in all cell lines. We have also found, by immunohistochemistry, cytoplasmic and surface expression of CTLA-4 in the tumor cells of all 6 osteosarcoma specimens examined and in the tumour cells of all 5 cases (but only weakly or no positivity at all in neighbouring nontumor cells) of ductal breast carcinomas. Treatment of cells from CTLA-4-expressing tumor lines with recombinant forms of the CTLA-4-ligands CD80 and CD86 induced apoptosis associated with sequential activation of caspase-8 and caspase-3. The level of apoptosis was reduced by soluble CTLA-4 and by anti-CTLA-4 scFvs antibodies. The novel finding that CTLA-4 molecule is expressed and functional on human tumor cells opens up the possibility of antitumor therapeutic intervention based on targeting this molecule.

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Metadata

Authors
Contardi, E., Palmisano, G. L., Tazzari, P. L., Martelli, A. M., Falà, F., Fabbi, M., Kato, T., Lucarelli, E., Donati, D., Polito, L., Bolognesi, A., Ricci, F., Salvi, S., Gargaglione, V., Mantero, S., Alberghini, M., Ferrara, G. B., & Pistillo, M. P.
Venue
International Journal of Cancer
Publisher
Wiley
Published
2005
Volume
117
Issue
4
Pages
538-550
ISSN
  • 0020-7136 (ISSN-L)
  • 1097-0215
OpenAlex
W1993851289
Cited by
324
References
47
FWCI
3.11
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. https://app.cochat.ai/papers/10.1002/ijc.21155
The paper
Contardi, E., Palmisano, G. L., Tazzari, P. L., Martelli, A. M., Falà, F., Fabbi, M., Kato, T., Lucarelli, E., Donati, D., Polito, L., Bolognesi, A., Ricci, F., Salvi, S., Gargaglione, V., Mantero, S., Alberghini, M., Ferrara, G. B., & Pistillo, M. P. (2005). CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. International Journal of Cancer. https://doi.org/10.1002/ijc.21155

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.