Hodgkin and Reed-Sternberg cell–associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells

Şahin, Uğur; Neumann, Frank; Türeci, Özlem; Schmits, Rudolf; Perez, Franck; Pfreundschuh, Michael

doi:10.1182/blood.v100.12.4139

Cited by 19 publications

(10 citation statements)

References 41 publications

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“…Similarly, functional IL-3Rs have been detected on normal B-cell precursors in the bone marrow [60] and on tumor cells from B-cell malignancies reflecting both early and late stages of B-cell lymphopoiesis such as B-lineage acute lymphoblastic leukemias [61 -63], follicular lymphomas [64,65], chronic lymphocytic leukemias [66], and malignant plasma cell precursors [67,68]. In addition to their B-lineage derivation, H -RS cells typically share several phenotypic and functional features with dendritic cells, including antigen-presenting capacity [4,69,70], expression of specific co-stimulatory molecules [3 -5, 69,70], cytoskeleton-associated proteins [69] and cytokine/chemokine profiles [3 -20]. Because IL-3 plays a pivotal role in the development of human dendritic cells, the demonstration of IL-3Ra on tumor cells of HD raises the possibility of a B lineage-oriented lymphoid dendritic cell progenitor as a putative normal counterpart of H -RS cells [71 -74].…”

Section: Expression Of Il-3r In Hdmentioning

confidence: 99%

The role of interleukin-3 in classical Hodgkin's disease

Aldinucci¹,

Olivo²,

Lorenzon³

et al. 2005

Leukemia & Lymphoma

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Classical Hodgkin's disease (HD) is a peculiar form of lymphoma characterized by a low frequency of tumor cells, the so-called Hodgkin (H) and Reed/Sternberg (RS) cells, embedded in a background of non-neoplastic (reactive) cells believed to be recruited and activated by H-RS cell-derived cytokines/chemokines. How these tumor cells can survive in such a seemingly hostile environment has confused researchers. We have previously identified interleukin (IL)-3 receptor (R) expression as a common feature of classical HD and unveiled the potential role of IL-3 as a growth and anti-apoptotic factor for H-RS cells. More then 90% of malignant cells of classical HD usually express the alpha chain of the IL-3R (IL-3R(alpha)), as evidenced by immunostaining of frozen sections and cell suspensions from neoplastic lymph nodes. Consistently, HD-derived cell lines (L428, KMH2, HDLM2 and L1236) express the alpha and beta chains that form IL-3R, both at the mRNA and protein level, with a molecular size of IL-3R(alpha) identical (70 kDa) to that expressed by human myeloid cells. Exogenous IL-3 promotes the growth of cultured H-RS cells, such an effect being potentiated by IL-9 and stem cell factor (SCF) co-stimulation, and is able to partially rescue tumor cells from apoptosis induced by serum deprivation. Finally, cultured H-RS cells are able to increase the production of IL-3 by pre-activated T cells, suggesting an involvement of IL-3/IL-3R interactions in the cellular growth of HD through paracrine mechanisms. This review will outline the biological activity of IL-3 and summarize the evidence indicating IL-3 as a growth and anti-apoptotic factor for H-RS cells in classical HD.

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Section: Expression Of Il-3r In Hdmentioning

confidence: 99%

The role of interleukin-3 in classical Hodgkin's disease

Aldinucci¹,

Olivo²,

Lorenzon³

et al. 2005

Leukemia & Lymphoma

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“…The etiology of Hodgkin lymphoma (HL) is unknown, but immunological and molecular properties suggest that HL cells are derived from B cells [1]–[3]. HL cells have a characteristic gene-expression profile that discriminates these cells from other normal and transformed hematopoietic cells [4], [5].…”

Section: Introductionmentioning

confidence: 99%

Knock-Down of PRAME Increases Retinoic Acid Signaling and Cytotoxic Drug Sensitivity of Hodgkin Lymphoma Cells

Kewitz

Staege

2013

PLoS ONE

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The prognosis for patients with Hodgkin lymphoma (HL) has improved in recent decades. On the other hand, not all patients can be cured with the currently established therapy regimes and this therapy is associated with several adverse late effects. Therefore it is necessary to develop new therapy strategies. After treatment of L-540 HL cells with 5′-azacytidine (5AC), we observed increased expression of the preferentially expressed antigen in melanoma (PRAME). In addition, we detected an increased resistance of 5AC-treated cells against cytotoxic drugs. We analyzed the influence of PRAME on cell survival of HL cells by knocking down PRAME in the chemotherapy resistant cell line L-428, a cell line that express PRAME at a high level. After knock-down of PRAME using vector based RNA interference we observed increased sensitivity for cisplatin, etoposide and retinoic acid. DNA microarray analysis of HL cells after PRAME knock-down indicated regulation of several genes including down-regulation of known anti-apoptotic factors. Increased retinoic acid signaling in these cells was revealed by increased expression of the retinoic acid metabolizing cytochrome P450 (CYP26B1), a transcriptional target of retinoic acid signaling. Our data suggest that PRAME inhibits retinoic acid signaling in HL cells and that the knock-down of PRAME might be an interesting option for the development of new therapy strategies for patients with chemo-resistant HL.

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“…According to their expression pattern and the specificity of the immune responses they evoke, antigens expressed by human neoplasms can be classified into different groups. 5 These include the so-called shared tumor antigens (e.g., the MAGE family), the differentiation antigens (e.g., tyrosinase), the products of viral genes (e.g., HPV-16), mutated genes (e.g., mutated p53), differentially spliced genes (e.g., restin 6 ), overexpressed genes and amplified genes (e.g., elF-4␥ 7 ) as well as common autoantigens that are expressed by the malignant cells of a tumor (e.g., U1 snRNP 5 ).…”

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Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis

Kubuschok

Xie

Jesnowski

et al. 2004

Intl Journal of Cancer

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In order to define antigens that might be suitable as vaccines for pancreatic carcinoma, we investigated the composite expression of 10 cancer testis (CT) antigens (SCP-1, NY-ESO-1, SSX-1, SSX-2, SSX-4, GAGE, MAGE-3, MAGE-4, CT-7 and CT-8) by Reverse Transcriptase-PCR (RT-PCR) in fresh biopsies of human pancreatic adenocarcinoma, chronic pancreatitis and pancreatic carcinoma cell lines. While all CT genes were frequently expressed in cell lines derived from pancreatic cancer, no expression of MAGE-3, SSX-1, SSX-2, NY-ESO-1 and CT-7 was detected in fresh tumor biopsies, and MAGE-4 (1/52), SSX-4 (1/39) and CT-8 (2/41) were only rarely expressed. In contrast, HOM-TES-14/SCP-1 was expressed in 48% (29/61) and GAGE in 21% (13/61) of cases, respectively. One CT gene was expressed by 59% (75% in male, 46% in female patients; p ‫؍‬ 0.05) and 2 or more CT genes by 15% of the samples. SCP-1 protein expression correlated well with mRNA expression. While SCP-1 and GAGE were absent in normal pancreas, they were found in 2/8 (SCP-1) and 1/8 (GAGE) samples of chronic pancreatitis, respectively, supporting the concept of chronic pancreatitis as a premalignant condition. SCP-1 and GAGE represent promising candidates for vaccine development in pancreatic carcinoma. Whether SCP-1 and GAGE expression identify cases of chronic pancreatitis with a high risk of malignant transformation remains to be shown. © 2004 Wiley-Liss, Inc. Key words: cancer testis antigen; tumor rejection antigen; MAGE; GAGE; SSX; NY-ESO-1; specific immunotherapy; cancer vaccineDespite recent advances in surgery, 1 radiotherapy 2 and chemotherapy 3 of pancreatic cancer, the 5-year survival remains 3-5% for all stages. 4 Therefore, alternative therapeutic approaches are pursued. Of the latter, immunotherapy has the potential of a therapeutic tool that might be integrated into conventional surgical, radiotherapeutic and chemotherapeutic treatment modalities without significantly adding to therapy-associated toxicity.A prerequisite for the development of tumor-specific immunotherapeutic strategies is the existence and identification of tumor antigens, i.e., genes that are either exclusively or preferentially expressed in malignant tissues compared to normal tissues. According to their expression pattern and the specificity of the immune responses they evoke, antigens expressed by human neoplasms can be classified into different groups. 5 These include the so-called shared tumor antigens (e.g., the MAGE family), the differentiation antigens (e.g., tyrosinase), the products of viral genes (e.g., HPV-16), mutated genes (e.g., mutated p53), differentially spliced genes (e.g., restin 6 ), overexpressed genes and amplified genes (e.g., elF-4␥ 7 ) as well as common autoantigens that are expressed by the malignant cells of a tumor (e.g., U1 snRNP 5 ).In pancreatic cancer, only few tumor antigens are known and most of them are overexpressed in tumor cells, but will also be found at a certain level in normal human cells (e.g., CEA, Her-2/ neu, MUC-1, CA19-9, CA 242 and 17-1...

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Hodgkin and Reed-Sternberg cell–associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells

Cited by 19 publications

References 41 publications

The role of interleukin-3 in classical Hodgkin's disease

The role of interleukin-3 in classical Hodgkin's disease

Knock-Down of PRAME Increases Retinoic Acid Signaling and Cytotoxic Drug Sensitivity of Hodgkin Lymphoma Cells

Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis

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