Identification of TRA‐1‐60‐positive cells as a potent refractory population in follicular lymphomas
| العنوان: | Identification of TRA‐1‐60‐positive cells as a potent refractory population in follicular lymphomas |
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| المؤلفون: | Satoshi Maruyama, Tadashi Yoshino, Yiwei Ling, Kennosuke Karube, Eisaku Kondo, Tomoko Miyata-Takata, Yukari Miki, Hidekazu Iioka, Christian Steidl, Yoshinobu Maeda, Shujiro Okuda, Ken Saito, Katsuyoshi Takata |
| المصدر: | Cancer Science |
| بيانات النشر: | John Wiley and Sons Inc., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Follicular lymphoma, Mice, SCID, Stem cell marker, rituximab, Mice, Inbred NOD, Antineoplastic Combined Chemotherapy Protocols, Pathology, Lymphoma, Follicular, Aged, 80 and over, education.field_of_study, General Medicine, Middle Aged, Tumor Burden, Gene Expression Regulation, Neoplastic, Oncology, Antigens, Surface, Rituximab, Original Article, Female, Proteoglycans, medicine.drug, Adult, Vincristine, Population, Transplantation, Heterologous, Biology, 03 medical and health sciences, follicular lymphoma, Cell Line, Tumor, medicine, Animals, Humans, education, Aged, Retrospective Studies, drug resistance, Gene Expression Profiling, Germinal center, Original Articles, medicine.disease, tumor recurrence, Lymphoma, TRA‐1‐60, 030104 developmental biology, Cell culture, Drug Resistance, Neoplasm, Cancer research |
| الوصف: | Despite receiving rituximab-combined chemotherapy, follicular lymphoma (FL) patients often suffer tumor recurrence and understand that the cause of relapse in FL would thus significantly ameliorate the tumor therapeutics. In the present study, we show that TRA-1-60-expressing cells are a unique population in FL, converge to the conventional stem cell marker Oct3/4 and ALDH1-positive population, and resist current B-lymphoma agents. TRA-1-60 expression was observed in scattered lymphoma cells in FL tissues only as well as in resting B-lymphocytes inside germinal centers. Retrospective comparison between recurrent and cognate primary tissues showed that the number of TRA-1-60-positive cells from rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP)-treated FL had increased relative to primary tissue, a finding corroborated by assays on different rituximab-treated FL cell lines, FL-18 and DOHH2, wherein TRA-positive cell numbers increased over 10-fold compared to the untreated sample. Concordantly, scanty TRA-1-60-positive FL-18 cells implanted s.c. into mice evinced potent tumor-initiating capacity in vivo, where tumors were 12-fold larger in volume (P = 0.0021 < 0.005) and 13-fold heavier in weight (P = 0.0015 < 0.005) compared to those xenografted from TRA-negative cells. To explain these results, gene expression profiling and qPCR analysis indicated that TRA-1-60-positive cells defined a distinct population from that of TRA-negative cells, with upregulation of multiple drug transporters and therapeutic resistance genes. Hence, TRA-1-60-expressing cells in FL are considered to be vigorously intractable against conventional therapeutic agents, which may explain its refractory recurrence. |
| اللغة: | English |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36cc064043260ce57d507fb8e6c3739cTest http://europepmc.org/articles/PMC6317956Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....36cc064043260ce57d507fb8e6c3739c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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