Project description:Breast cancer cells (BCCs) can remain undetected for decades in dormancy. These quiescent cells are similar to cancer stem cells (CSCs); hence their ability to initiate tertiary metastasis. Dormancy can be regulated by components of the tissue microenvironment such as bone marrow mesenchymal stem cells (MSCs) that release exosomes to dediferentiate BCCs into CSCs. The exosomes cargo includes histone 3, lysine 4 (H3K4) methyltransferases - KMT2B and KMT2D. A less studied mechanism of CSC maintenance is the process of cell-autonomous regulation, leading us to examine the roles for KMT2B and KMT2D in sustaining CSCs, and their potential as drug targets.
Project description:We hypothesized that miRNAs in the bone maroow mesenchymal stem cells (BM-MSC)-derived exosomes contributed to the phenotype change of breast cancer cells through exosome transfer. We analyzed the miRNA expression signature in BM-MSC-derived exosomes. We compared the miRNA expression levels in exosomes between BM-MSCs and adult fibroblasts (as a control). In this study, miRNA expression including in bone-marrow mesenchymal cell (BM-MSC)-derived exosomes was examined, and compared with that of exosomes derived from adult fibroblast cells or the BM-MSC cells. In addition, miRNA expression of BM-MSC exosomes was also compared with that of breast cancer cells with or without cancer stem cell marker.
Project description:Transcription profiling of human bone marrow mesenchymal stem cells treated with exosomes isolated from chronic lymphocytic leukemia cell line MEC-1 supernatant. Cells were left untreated or treated with CLL-exosomes for 6h at 37C.
Project description:Despite widespread knowledge that bone marrow-resident breast cancer cells (BMRCs) affect tumor progression, signaling mechanisms of BMRCs implicated in maintaining long-term dormancy have not been characterized. To overcome these hurdles, we developed a novel experimental model of tumor dormancy employing circulating tumor cells (CTCs) derived from metastatic breast cancer patients (de novo CTCs), transplanted them in immunocompromised mice, and re-isolated these cells from xenografted mice bone marrow (ex vivo BMRCs) and blood (ex vivo CTCs) to perform downstream transcriptomic analyses. Here we report that the balance between mTORC1 vs mTORC2 signaling regulates BMRC mitotic and/or dormancy characteristics.
Project description:Mesenchymal stromal cells (MSCs) are multipotent cells that reside in various tissues, including bone marrow, adipose tissue or dental pulp. They can differentiate into different cell lineages, including osteoblasts, chondrocytes, and adipocytes. MSCs are recruited and stimulate the progression of renal cancer. However, the exact mechanisms that govern MSCs homing to renal tumors are largely unknown. Here, we found that renal cancer cells secrete piR_004153 encapsulated in exosomes that are taken-up by MSCs to induce transcriptional reprograming, and stimulate their migration towards renal cancer cells. To explore the impact of piRNA on MSCs, we transfected them with piR_004153 or non-targeting scrambled control oligonucleotide and analyzed their transcriptome using microarrays.
Project description:Human induced pluripotent stem cells provide an unlimited, scalable source of youthful tissue progenitors and secretome for regenerative therapies. The aim of our study was to assess the potential of conditioned medium (CM) derived from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of adult and aged human bone marrow-mesenchymal stromal cells (MSCs). In addition, we evaluated whether extended cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the CM stimulatory activity.
Project description:We performed gene expression profiling of bone marrow-mesenchymal cells (BM-MSCs) isolated from BALB/c and NeuT mice at 12 and 24 weeks of age, representative of early and late stages of breast cancer tumorigenesis, respectively.
Project description:We hypothesized that miRNAs in the bone maroow mesenchymal stem cells (BM-MSC)-derived exosomes contributed to the phenotype change of breast cancer cells through exosome transfer. We analyzed the miRNA expression signature in BM-MSC-derived exosomes. We compared the miRNA expression levels in exosomes between BM-MSCs and adult fibroblasts (as a control).
Project description:Breast tumour cells were found to remodel the bone marrow vascular microenviornment to support metastatic expansion. To identify tumour-derived factors that stimulate marrow endothelium, we studied the transcriptomes of four isogenic murine mammary tumour cell lines, 4T1.2, 4T1, 66cl4 and 67NR.
2021-09-16 | GSE160101 | GEO
Project description:miRNA expression profiles in bone marrow mesenchymal stem cell-derived exosomes
