RNA-seq of Highly Metastatic and Lowly Metastatic 4T1 Single Clones Treated with Iron Chelator Deferasirox (DFX)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE218133 | GEO | 2022/11/16
REPOSITORIES: GEO
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Project description:Deferasirox (DFX) is an oral iron chelator used to reduce iron overload caused by frequent red blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study molecular mechanisms by which DFX improves outcome in MDS, we analyzed gene expression patterns in MDS patients before and after DFX therapy.
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Project description:This laboratory's focus is on the immune response to carbohydrate antigens, with an emphasis on modalities to analyze and to increase the immune response. We are also interested in carbohydrate drug targeting. The hypothesis is that these 2 variants have different cell surface carbohydrate expression, which results in different adhesion patterns, which ultimately results in different metastasis patterns. Evidence for expression differences and loss of the variants ability to metastasize to the lung could have clinical implications in the prevention of metastasis to different organs. The 4T1 mouse metastatic breast cancer cell line is known to change with passages in culture. Our data has shown changes cause the cells to metastasize to the intestine rather than to the lung. Four classes of RNA were analyzed: one each from 4T1 metastatic cell line variant #1, 4T1 variant #2, non-metastatic cell lines 4T07, and non-metastatic cell line 67NR. Classes were prepared in triplicate for a total of 12 samples. All samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.
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Project description:A polyclonal mouse model of breast tumor heterogeneity using model cell line 4T1 was developed previously. It was shown that 4T1 cells were composed of mixed subpopulations with specializations, including dominating the primary tumor, contributing to metastatic populations, etc. Here in a different angle, we reveal that each 4T1 cells can switch between 2 distinct states, which could be easily misclassified into 2 subpopulations, as the 2 states can be distinguished by distinct patterns of gene expression, dramatic difference of metastatic competence, stem-cell like feature or not, etc. The event for each 4T1 cell to exhibit one state or another is stochastic and the metastatic competence of clones generated from a single 4T1 cell is variable rather than stable. Further, given that metastatic competence of 4T1 cells is not stable, classification of clones based on metastatic competence is highly biased. Similarly, the classification of 4T1 clones based on gene expression profiles is also highly biased. Taken together, our data support that the exhibition of metastatic competence depends on the state of 4T1 cells and do not support the existence of subpopulations with specialization. To the best of our knowledge, no similar work has ever been reported.
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