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Immunophenotypic characterization of sphere-forming cells derived from the human renal cell carcinoma cell line 786-O.

ABSTRACT: Cancer stem cells (CSCs) have been found in many different types of malignant tumors. In our previous study, we found that sphere-forming cells (SFCs) from the renal cell carcinoma (RCC) cell line SK-RC-42 are rich in CSCs. However, our previous reports are based on only one human RCC cell line, which makes it difficult to determine whether the findings from this cell line represent the general mechanisms in human RCC. Therefore, in this study, we attempted to evaluate whether the sphere culture method could enrich for CSCs from another human RCC cell line, 786-O, and to characterize their immunological phenotype. We discovered that a small population of 786-O cells was capable of growing as tumor spheres. The SFCs had many properties similar to CSCs, including greater ability to self-renew in vitro and in vivo, higher mRNA expression levels of several 'stemness' genes, stronger tumorigenicity and resistance to chemotherapeutic agents than monolayer adherent cells (MACs). The SFCs expressed low levels of MHC-I, HLA-DR, CD80, CD86, CD152 and CD154. Additionally, the SFCs had lower expression levels of Her2 and hTERT, FasL, Fas, the transcription factor forkhead box protein 3 (FoxP3) and activating natural killer cell receptors than did the MACs. In addition, both 786-O SFCs and MACs were weakly positive for B7-H4 expression, while the expression level of B7-H1 in 786-O SFCs was lower than that in MACs. Furthermore, 786-O SFCs and MACs both expressed substantial and comparable levels of membrane complement regulatory proteins (mCRPs). Finally, we found that 786-O SFCs triggered T cell apoptosis. These findings suggested that tumor spheres from 786-O cells are rich in CSCs. The immunological phenotype of the SFCs described in our study suggests that CSCs might play an important role in tumor immune evasion.

SUBMITTER: Shen C

PROVIDER: S-EPMC6325489 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Immunophenotypic characterization of sphere-forming cells derived from the human renal cell carcinoma cell line 786-O.

Shen Chanjuan C Hu Guoyu G Zhang Shuren S Ao Xiang X Zhou Qiaoling Q Xiao Ping P Zhong Yong Y

American journal of translational research 20181215 12

Cancer stem cells (CSCs) have been found in many different types of malignant tumors. In our previous study, we found that sphere-forming cells (SFCs) from the renal cell carcinoma (RCC) cell line SK-RC-42 are rich in CSCs. However, our previous reports are based on only one human RCC cell line, which makes it difficult to determine whether the findings from this cell line represent the general mechanisms in human RCC. Therefore, in this study, we attempted to evaluate whether the sphere culture ...[more]

PMID: 30662644

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Project description:The phenotypic diversity of breast carcinoma may be explained by the existence of a sub-population of breast cancer cells, endowed with stem cell-like properties and gene expression profiles, able to differentiate along different pathways. A stem cell-like population of CD44(+)CD24(-/low) breast cancer cells was originally identified using cells from metastatic pleural effusions of breast carcinoma patients. We have previously reported that upon in vitro culture as mammospheres under stem cell-like conditions, human MA-11 breast carcinoma cells acquired increased tumorigenicity and lost CD24 expression compared with the parental cell line. We now report that upon passage of MA-11 mammospheres into serum-supplemented cultures, CD24 expression was restored; the rapid increase in CD24 expression was consistent with up-regulation of the antigen, and not with in vitro selection of CD24(+) cells. In tumors derived from subcutaneous injection of MA-11 mammospheres in athymic nude mice, 76.1+/-9.7% of cells expressed CD24, vs. 0.5+/-1% in MA-11 cells dissociated from mammospheres before injection. The tumorigenicity of sorted CD44(+)CD24(-) and CD44(+)CD24(high) MA-11 cells was equal. Single cell-sorted CD24(-) and CD24(high) MA-11 gave rise in vitro to cell populations with heterogeneous CD24 expression. Also, subcutaneous tumors derived from sorted CD24(-) sub-populations and single-cell clones had levels of CD24 expression similar to the unsorted cells. To investigate whether the high expression of CD24 contributed to the tumorigenic potential of MA-11 cells, we silenced CD24 by shRNA. CD24 silencing (95%) resulted in no difference in tumorigenicity upon s.c. injection in athymic nude mice compared with mock-transduced MA-11 cells. Since CD24 silencing was maintained in vivo, our data suggest that the level of expression of CD24 is associated with but does not contribute to tumorigenicity. We then compared the molecular profile of the mammospheres with the adherent cell fraction. Gene expression profiling revealed that the increased tumorigenicity of MA-11 mammospheres was associated with changes in 10 signal transduction pathways, including MAP kinase, Notch and Wnt, and increased expression of aldehyde dehydrogenase, a cancer-initiating cell-associated marker. Our data demonstrate that (i) the level of CD24 expression is neither a stable feature of mammosphere-forming cells nor confers tumorigenic potential to MA-11 cells; (ii) cancer-initiating cell-enriched MA-11 mammospheres have activated specific signal transduction pathways, potential targets for anti-breast cancer therapy.

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Immunophenotypic characterization of sphere-forming cells derived from the human renal cell carcinoma cell line 786-O.

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Immunophenotypic characterization of sphere-forming cells derived from the human renal cell carcinoma cell line 786-O.

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