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1.
Cell Biol Int ; 38(11): 1252-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24889971

RESUMO

Iron uptake by the transferrin (Tf)-transferrin receptor (TfR) complex is critical for erythroid differentiation. The mechanisms of TfR trafficking have been examined, but the adaptor proteins involved in this process are not fully elucidated. We have investigated the role of the adaptor protein, Disabled-2 (Dab2), in erythroid differentiation and Tf uptake in the cells of hematopoietic lineage. Dab2 was upregulated in a time-dependent manner during erythroid differentiation of mouse embryonic stem cells and human K562 erythroleukemic cells. Attenuating Dab2 expression in K562 cells diminished TfR internalization and increased surface levels of TfR concomitantly with a decrease in Tf uptake and erythroid differentiation. Dab2 regulated Tf uptake of the suspended, but not adherent, cultures of K562 cells. In contrast, Dab2 is not involved in TfR trafficking in the HeLa cells with epithelial origin. These differential effects are Dab2-specific because attenuating the expression of adaptor protein 2 µ subunit inhibited the uptake of Tf regardless of culture condition. We offer novel insight of Dab2 function in iron uptake and TfR internalization for the suspended culture of hematopoietic lineage cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transferrina/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células-Tronco Embrionárias/citologia , Eritrócitos/citologia , Células HeLa , Humanos , Hidroxiureia/farmacologia , Células K562 , Camundongos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores da Transferrina/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Regulação para Cima
2.
Biomed J ; 43(2): 146-162, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32441651

RESUMO

BACKGROUND: Podoplanin (PDPN) is a transmembrane glycoprotein that mediates tumor cell-induced platelets aggregation in different cancer types. Emerging data indicate that PDPN is a marker for poor prognosis of human oral squamous cell carcinoma (OSCC). However, the functional impacts of PDPN on cancer formation and disease progression of OSCC remain to be elucidated. METHODS: The sublines of the OECM-1 oral cancer cells with PDPN knockdown or overexpression were established. The cellular characteristics and the ability to induce platelet aggregation of these cells lines were analyzed. An ectopic xenograft animal model by inoculating cancer cells into the anterior neck region of nude mice was established to investigate the functional impact of PDPN on disease progression and cancer-associated thrombosis of OSCC. RESULTS: PDPN promoted OSCC cell migration and invasion, but had no effect on cell proliferation in vitro and tumor growth in vivo. Co-incubation of PDPN-positive (PDPN+) OSCC cells with platelets induced platelet activation and aggregation. The mice bearing PDPN+ tumor had a decrease in overall survival despite that there was no gross appearance of distant metastasis. A speckled immunofluorescence staining pattern of platelet marker mCD41 was defined in the PDPN+ tumor sections and the intensity was greater than in the PDPN-low or negative tumor sections. Co-immunofluorescence staining of the tumor sections with mCD41 and the endothelial cell marker mCD31 further demonstrated that platelet aggregates were located in the lumen of blood vessel and were also distributed intratumorally in the mice bearing PDPN+ tumors. CONCLUSIONS: These data demonstrated that PDPN expression in the cancer cells is associated with high risk of thrombosis, leading to unfavorable overall survival of the mice. This study provides new insights into the functions of PDPN in cancer-associated thrombosis and in the pathophysiology of OSCC.


Assuntos
Glicoproteínas de Membrana/farmacologia , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Trombose/induzido quimicamente , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Xenoenxertos/patologia , Humanos , Glicoproteínas de Membrana/metabolismo , Camundongos Nus , Agregação Plaquetária/efeitos dos fármacos
3.
Thyroid ; 28(11): 1479-1489, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30221579

RESUMO

BACKGROUND: Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer. METHODS: Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses. RESULTS: The EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively. CONCLUSIONS: CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.


Assuntos
Células Epiteliais/metabolismo , Recidiva Local de Neoplasia/metabolismo , Células Neoplásicas Circulantes/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Molécula de Adesão da Célula Epitelial/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Receptores da Tireotropina/metabolismo , Taxa de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
4.
FEBS Lett ; 588(1): 58-64, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24239537

RESUMO

Reelin is an extracellular glycoprotein that is highly conserved in mammals. In addition to its expression in the nervous system, Reelin is present in erythroid cells but its function there is unknown. We report in this study that Reelin is up-regulated during erythroid differentiation of human erythroleukemic K562 cells and is expressed in the erythroid progenitors of murine bone marrow. Reelin deficiency promotes erythroid differentiation of K562 cells and augments erythroid production in murine bone marrow. In accordance with these findings, Reelin deficiency attenuates AKT phosphorylation of the Ter119(+)CD71(+) erythroid progenitors and alters the cell number and frequency of the progenitors at different erythroid differentiation stages. A regulatory role of Reelin in erythroid differentiation is thus defined.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Diferenciação Celular , Células Eritroides/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Serina Endopeptidases/metabolismo , Animais , Western Blotting , Células da Medula Óssea/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Linhagem da Célula/genética , Células Precursoras Eritroides/metabolismo , Proteínas da Matriz Extracelular/genética , Regulação Leucêmica da Expressão Gênica , Homozigoto , Humanos , Células K562 , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/metabolismo , Camundongos , Camundongos Mutantes Neurológicos , Proteínas do Tecido Nervoso/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Proteína Reelina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina Endopeptidases/genética , Regulação para Cima
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