In vitro characterization of CD133lo cancer stem cells in Retinoblastoma Y79 cell line

Nair, Rohini; Balla, Murali Mohan Sagar; Khan, Imran; Kalathur, Ravi Kiran Reddy; Kondaiah, Paturu; Vemuganti, Geeta K.

doi:10.1186/s12885-017-3750-2

Cited by 31 publications

(34 citation statements)

References 43 publications

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“…We further investigated the expression of CSC-related genes in CRC cells after treatment with Treg supernatants. The results showed that CSC-related gene [25, 26] expression in SW620 and DLD1 cells was significantly lower than that in cells treated with Treg supernatants (Fig. 4d).…”

Section: Resultsmentioning

confidence: 94%

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

Wang¹,

Yang²,

Yu³

et al. 2019

j. immunotherapy cancer

159

116

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Background Colorectal cancer (CRC) is one of the most common forms of cancer worldwide. The tumor microenvironment plays a key role in promoting the occurrence of chemoresistance in solid cancers. Effective targets to overcome resistance are necessary to improve the survival and prognosis of CRC patients. This study aimed to evaluate the molecular mechanisms of the tumor microenvironment that might be involved in chemoresistance in patients with CRC. Methods We evaluated the effects of CCL20 on chemoresistance of CRC by recruitment of regulatory T cells (Tregs) in vitro and in vivo. Results We found that the level of CCL20 derived from tumor cells was significantly higher in Folfox-resistant patients than in Folfox-sensitive patients. The high level of CCL20 was closely associated with chemoresistance and poor survival in CRC patients. Among the drugs in Folfox chemotherapy, we confirmed that 5-FU increased the expression of CCL20 in CRC. Moreover, CCL20 derived from 5-FU-resistant CRC cells promoted recruitment of Tregs. Tregs further enhanced the chemoresistance of CRC cells to 5-FU. FOXO1/CEBPB/NF-κB signaling was activated in CRC cells after 5-FU treatment and was required for CCL20 upregulation mediated by 5-FU. Furthermore, CCL20 blockade suppressed tumor progression and restored 5-FU sensitivity in CRC. Lastly, the expression of these signaling molecules mediating chemoresistance was closely correlated with poor survival of CRC patients. Conclusions CRC cell-secreted CCL20 can recruit Tregs to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling, indicating that the FOXO1/CEBPB/NF-κB/CCL20 axis might provide a promising target for CRC treatment. Electronic supplementary material The online version of this article (10.1186/s40425-019-0701-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 94%

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

Wang¹,

Yang²,

Yu³

et al. 2019

j. immunotherapy cancer

159

116

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“…Besides glioblastoma, SDF-1/CXCR4 signaling has been shown to be functional in stem(-like) subpopulations of retinoblastoma (60), melanoma (61), pancreatic ductal adenocarcinoma (62), non-small cell lung cancer (63), cervical carcinoma (64), prostate cancer (65), head and neck squamous cell carcinoma (66), rhabdomyosarcoma (67, 68), synovial sarcoma (56), and leukemia (69). In summary, these data might hint to an ontogenetically early onset of SDF-1/CXCR4 signaling in mesenchymal and epithelial primordia of the different organs which might be the reason for SDF-1/CXCR4 expression in stem(-like) subpopulations of many different tumor entities.…”

Section: Sdf-1/cxcr4 Function In Tumor Biologymentioning

confidence: 99%

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

Schilbach²,

et al. 2018

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Cancer immunotherapy has been established as standard of care in different tumor entities. After the first reports on synergistic effects with radiotherapy and the induction of abscopal effects—tumor shrinkage outside the irradiated volume attributed to immunological effects of radiotherapy—several treatment combinations have been evaluated. Different immunotherapy strategies (e.g., immune checkpoint inhibition, vaccination, cytokine based therapies) have been combined with local tumor irradiation in preclinical models. Clinical trials are ongoing in different cancer entities with a broad range of immunotherapeutics and radiation schedules. SDF-1 (CXCL12)/CXCR4 signaling has been described to play a major role in tumor biology, especially in hypoxia adaptation, metastasis and migration. Local tumor irradiation is a known inducer of SDF-1 expression and release. CXCR4 also plays a major role in immunological processes. CXCR4 antagonists have been approved for the use of hematopoietic stem cell mobilization from the bone marrow. In addition, several groups reported an influence of the SDF-1/CXCR4 axis on intratumoral immune cell subsets and anti-tumor immune response. The aim of this review is to merge the knowledge on the role of SDF-1/CXCR4 in tumor biology, radiotherapy and immunotherapy of cancer and in combinatorial approaches.

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“…Many tumors contain a small percentage of cancer stem cells, with the ability to self-renew, metastasize, and confer chemoresistance (for review see [21]). Previous work from our group, confirmed by others, has demonstrated the presence of these cancer stem cell markers in human retinoblastoma [22,23,24,25]. We know that in breast cancer, Her2 expression and overexpression is associated with a cancer stem cell phenotype (for Review, see [26]).…”

Section: Discussionmentioning

confidence: 62%

In situ analysis of Her2 DNA and RNA in retinoblastoma and adjacent retina

et al. 2019

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Retinoblastoma (RB) is an ocular tumor of early childhood. Current treatments attempt to preserve visual function, but may spare chemoresistant tumor cells. One potential therapeutic target for RB is HER2, (ERBB2), expressed in RB in truncated form. In this study, we tested the hypothesis that Her2 DNA and RNA are expressed in RB tumors and adjacent retina. We examined 24 human RB tumors as well as normal-appearing adjacent retinal tissues for Her2 DNA and RNA expression by in situ hybridization. We also examined 28 RB tumors for HER2 protein immunoreactivity. 21/22 RB tumors expressed Her2 DNA and 14/19 tumors expressed Her2 RNA. In 17 paired cases, there were three cases in which Her2 DNA was detected, but not RNA. We also saw Her2 RNA signal in six instances of “normal” adjacent retinal tissue. Heterogeneous HER2 protein expression in specific tumor regions also was confirmed by quantitative HER2 immunohistochemistry. In summary, Her2 DNA and RNA are expressed in many RB tumors, and in some adjacent ocular tissues, with hetereogenous protein expression throughout. These results may provide important insights regarding RB tumor progression, and drug targeting approaches designed to spare the eye, preserve vision and improve quality of life for RB patients.

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In vitro characterization of CD133lo cancer stem cells in Retinoblastoma Y79 cell line

Cited by 31 publications

References 43 publications

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

In situ analysis of Her2 DNA and RNA in retinoblastoma and adjacent retina

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