RESUMO
BACKGROUND: BAFF and APRIL share two receptors - TACI and BCMA - and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. METHODS: We compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types - brain, epithelial, lymphoid, germ cells - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. RESULTS: We found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans. CONCLUSION: Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.
Assuntos
Carcinoma/metabolismo , Linfoma/metabolismo , Mieloma Múltiplo/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Fator Ativador de Células B/genética , Fator Ativador de Células B/imunologia , Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/patologia , Proliferação de Células , Sobrevivência Celular , Difenilamina/análogos & derivados , Difenilamina/imunologia , Difenilamina/metabolismo , Progressão da Doença , Heparina/análogos & derivados , Heparina/genética , Heparina/imunologia , Heparina/metabolismo , Humanos , Linfoma/genética , Linfoma/imunologia , Linfoma/patologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Ligação Proteica , Proteoglicanas/genética , Proteoglicanas/imunologia , Proteoglicanas/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Proteína Transmembrana Ativadora e Interagente do CAML/genética , Proteína Transmembrana Ativadora e Interagente do CAML/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologiaRESUMO
A potent antischistosomal drug, Amoscanate, was found to be immunogenic to mice and Cebus apella monkeys. The drug was readily haptenated to proteins under relatively mild conditions. The Amoscanate-protein conjugates were observed to be immunogenic when injected into the footpads of several strains of mice. However, such protein conjugates were not found to raise IgE antibody to the drug in high-responder strains using several procedures. When the formulated drug (dissolved in oil) was fed to CD 1 mice, a rise in serum antibody against the drug was noted 1 week following the primary dose. This is preliminary evidence that the drug, or a cross-reactive metabolite, becomes covalently bound to proteins in vivo. Cebus apella monkeys fed the drug exhibited a rise in anti-Amoscanate antibody one month after a second oral dose. These data suggest that the immunogenicity of Amoscanate is readily detected; furthermore, since there is no lasting immunity to schistosomiasis, thus necessitating multiple administration of the drug, the possibility that serum antibody titers to Amoscanate may interfere with its therapeutic efficacy cannot be overlooked.
Assuntos
Compostos de Anilina/imunologia , Anticorpos/análise , Difenilamina/imunologia , Isotiocianatos , Esquistossomicidas/imunologia , Tiocianatos/imunologia , Animais , Cebus , Difenilamina/análogos & derivados , Relação Dose-Resposta Imunológica , Epitopos/análise , Eritromicina/farmacologia , Feminino , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Coelhos , Ratos , Ratos Endogâmicos , Reaginas/análise , EspectrofotometriaRESUMO
A potent antischistosomal drug, Amoscanate, was found to induce vigorous serum antibody responses when either fed or administered parenterally as a drug-protein conjugate. Because of preliminary evidence that the drug could bind covalently to proteins in vivo, we decided to investigate the possibility that the drug could act as a contact sensitizing agent like DNCB. It was found that Amoscanate could induce a delayed-type hypersensitivity (DTH) response when painted on the shaved skin of guinea pigs. Moreover, the type of DTH response elicited was found to be cutaneous basophilic hypersensitivity (CBH). The significance of these findings are discussed.