Human Urinary Bladder Transitional Cell Carcinomas Acquire the Functional Fas Ligand during Tumor Progression

Chopin, Dominique; Barei-Moniri, Reza; Maillé, Pascale; Frère‐Belda, Marie‐Aude Le; Muscatelli-Groux, Béatrice; Merendino, Nicolò; Lecerf, Laure; Stoppacciaro, Antonella; Velotti, Francesca

doi:10.1016/s0002-9440(10)63910-7

Cited by 32 publications

(17 citation statements)

References 32 publications

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“…Another aspect of the Fas -FasL system is FasL expression in cancer cells. Recently, Chopin et al (2003) reported FasL expression in a series of 44 UC specimens and showed that UC acquired a functional FasL with progression to a higher grade and stage. They applied A11 and H11 (Alexis, Lausen, CH) clones of FasL antibodies for immunohistochemical staining in this rather small patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

et al. 2005

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The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas -FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (Po0.0001), a more advanced stage (P ¼ 0.023) and poorer prognosis (P ¼ 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

et al. 2005

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“…The RT4, UM‐UC‐3, RT112, SD48, TCCSUP, T24, 5637, EJ, J82 and SCaBER human bladder cancer cell lines were obtained from originators' laboratories or ATCC (Rockville, MD); 1512 and 1207 were developed as previously described 34. YT‐S, a human cytotoxic NK leukemia cell line, served as positive control.…”

Section: Methodsmentioning

confidence: 99%

Granzyme B is expressed in urothelial carcinoma and promotes cancer cell invasion

D'Eliseo

Pisu

Romano

et al. 2010

Intl Journal of Cancer

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Granzyme B (GrB) is a serine proteinase known to be expressed by cytotoxic lymphocytes and to induce, in presence of perforin (Pf), apoptosis in target cells. Recently, GrB expression has been shown (often in absence of Pf) in nonlymphoid cells, but its function is not defined. In our study, we investigated GrB and Pf expression in bladder cancer cell lines and in urothelial carcinoma (UC) tissues by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, ELISA, immunofluorescence and immunohistochemistry. We also assessed the function of GrB in UC cells; the in vitro function of GrB was examined by loss-of-function experiments. Our results revealed that GrB is expressed, in absence of Pf, in UC cells. Significant differences were found between GrB expression and both increasing pathological tumor spreading and high-grade vs. low-grade pTa tumors. Notably, GrB in UC tissues was concentrated at the cancer invasion front and was expressed in neoplastic cells undergoing epithelial-mesenchymal transition, a key event in carcinoma invasion. Indeed, GrB-positive cells also expressed Snail, N-cadherin or were negative for E-cadherin. GrB expressed in tumor cell lines was enzymatically active and capable of vitronectin cleavage, implying extracellular matrix (ECM) remodeling by GrB. Inhibition of GrB activity or Stealth RNA interference-mediated GrB gene silencing markedly suppressed bladder cancer cell invasion through matrigel. This data provides the first evidence for a role of GrB in promoting cancer cell invasion. Taken together, our findings suggest that GrB, via ECM degradation, contributes to the establishment of the UC invasive phenotype.

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“…The human 1512 short-term cultured urinary bladder transitional-cell carcinoma (TCC) cell line was generated by direct culturing of a resected bladder TCC tissue (33). The human T24, J82, and SD48 long-term established bladder TCC cell lines were obtained from originators' laboratories or from American Type Culture Collection.…”

Section: Cell Lines Tumors and Synthetic Peptidesmentioning

confidence: 99%

The Use of Filamentous Bacteriophagefdto Deliver MAGE-A10 or MAGE-A3 HLA-A2-Restricted Peptides and to Induce Strong Antitumor CTL Responses

Sartorius

Pisu

D’Apice

et al. 2008

The Journal of Immunology

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Delivery of tumor-associated Ag-derived peptides in a high immunogenic form represents one of the key issues for effective peptide-based cancer vaccine development. We report herein the ability of nonpathogenic filamentous bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10254–262- or MAGE-A3271–279-derived peptides and to elicit potent specific CTL responses in vitro and in vivo. Interestingly, human anti-MAGE-A3271–279-specific CTLs were able to kill human MAGE-A3+ tumor cells, even if these cells naturally express a low amount of MAGE-A3271–279 peptide-HLA epitope surface complexes and are usually not recognized by CTLs generated by conventional stimulation procedures. MAGE-A3271–279-specific/CD8+ CTL clones were isolated from in vitro cultures, and their high avidity for Ag recognition was assessed. Moreover, in vivo tumor protection assay showed that vaccination of humanized HHD (HLA-A2.1+/H2-Db+) transgenic mice with phage particles expressing MAGE-A3271–279-derived peptides hampered tumor growth. Overall, these data indicate that engineered filamentous bacteriophage virions increase substantially the immunogenicity of delivered tumor-associated Ag-derived peptides, thus representing a novel powerful system for the development of effective peptide-based cancer vaccines.

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Human Urinary Bladder Transitional Cell Carcinomas Acquire the Functional Fas Ligand during Tumor Progression

Cited by 32 publications

References 32 publications

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

Granzyme B is expressed in urothelial carcinoma and promotes cancer cell invasion

The Use of Filamentous Bacteriophagefdto Deliver MAGE-A10 or MAGE-A3 HLA-A2-Restricted Peptides and to Induce Strong Antitumor CTL Responses

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