RESUMO
OBJECTIVES: Angiogenesis and neovascularisation plays a crucial role for tumorigenesis and tumor progression in head and neck squamous cell carcinoma (HNSCC). The aim of our study was to investigate the neovascularization capacity by endothelial progenitor cells (EPC) in tumor patient as a possible predictor for tumor progression and tumor stage. MATERIALS AND METHODS: Therefore, we investigated the cell number and biologic activity by cell migration and colony-forming ability of EPC. Cells were isolated from the peripheral venous blood of 79 patients who suffer HNSCC in different stages of disease. Thirty-three healthy individuals served as the control group. RESULTS: Significantly increased biological activities were reflected by expression of the migration rate (1027 ± 1510) in comparison to the control group (632 ± 269) and the clonal potency measured by colony-forming unit (CFU) (tumor patients (19.7 ± 12.3) vs. control group (10.84 ± 4.8)). To determine whether or not EPC number can be used as a valid prognostic marker for clinical outcome of tumor patients, we furthermore compared a "high EPC-number-subgroup" (HI) with a "low EPC-number-subgroup" (LO) in a Kaplan-Meier survival curve. The HI-subgroup shows herein clearly a worse outcome. CONCLUSIONS: Our findings indicate a possible pathway for EPC to play a critical role in the vasculogenesis and consequently in the progression of HNSCC. CLINICAL RELEVANCE: Our findings could serve as possible predictors for the neovascularisation potential in HNSCC tumor patients.
Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Células Progenitoras Endoteliais/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neovascularização Patológica/patologia , Idoso , Biomarcadores Tumorais , Estudos de Casos e Controles , Movimento Celular , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Células-TroncoRESUMO
BACKGROUND: Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses. OBJECTIVE: Genetic inactivation of the murine CR2 locus results in impaired humoral immune responses. Here we report the first case of a genetic CD21 deficiency in human subjects. METHODS: CD21 protein expression was analyzed by means of flow cytometry and Western blotting. CD21 transcripts were quantified by using real-time PCR. The CD21 gene was sequenced. Wild-type and mutant CD21 cDNA expression was studied after transfection of 293T cells. Binding of EBV-gp350 or C3d-containing immune complexes and induction of calcium flux in CD21-deficient B cells were analyzed by means of flow cytometry. Antibody responses to protein and polysaccharide vaccines were measured. RESULTS: A 28-year-old man presented with recurrent infections, reduced class-switched memory B cells, and hypogammaglobulinemia. CD21 receptor expression was undetectable. Binding of C3d-containing immune complexes and EBV-gp350 to B cells was severely reduced. Sequence analysis revealed a compound heterozygous deleterious mutation in the CD21 gene. Functional studies with anti-immunoglobulin- and C3d-containing immune complexes showed a complete loss of costimulatory activity of C3d in enhancing suboptimal B-cell receptor stimulation. Vaccination responses to protein antigens were normal, but the response to pneumococcal polysaccharide vaccination was moderately impaired. CONCLUSIONS: Genetic CD21 deficiency adds to the molecular defects observed in human subjects with hypogammaglobulinemia.