Single cell RNA analysis of breast cancer bone metastases
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ABSTRACT:
PROVIDER: PRJNA788457 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:For single cell RNA sequencing analysis, whole cell population isolated from two breast cancer bone metastases and associated organoid models were analyzed by 10X genomic single cell RNA platform. Raw BCL files from Novaseq6000 was converted to FASTQ files with cellranger (Version: 3.1.0) mkfastq function. Cellranger count function was then applied for read alignment, barcode and UMI counting using GRCh38 as reference. scCB2 and DoubletFinder were used to predict and remove empty droplets and doublets of single cell data. Cells with number of features less 300 and more than 9000 were further filtered out based on the distribution of number of features. For bulk RNA sequencing, RNA were extracted from FFPE preserved primary tumor and bone metastasis. Library was prepared with TruSeq Stranded mRNA for FFPE kit, and sequenced by NextSeq 500 with high output 150 cycle kit.
2022-02-08 | GSE190772 | GEO
Project description:Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, we undertook RNA sequencing of circulating tumor cells (CTCs) obtained from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is Androgen Receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splicing variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it may contribute to acquired resistance to anti-estrogen therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER+ breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.
2018-02-19 | GSE86978 | GEO
Project description:We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from breast cancer patients with only bone metastases and metastases in bone and visceral organs. We collected bone metastases biopsies from breast cancer patients with only bone metastases and metastases in bone and visceral organs. RNA was extracted from these samples and subjected to microarray analysis with the Agilent platform. Data were compared with a signsture obtained with the Affymetrix platform, to obtain a signature of differentially regulated genes between the two groups of patients This Series represents the Agilent data only. The Affymetrix data are provided in GEO Series GSE11078.
2011-12-29 | E-GEOD-34485 | biostudies-arrayexpress
Project description:We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from breast cancer patients with only bone metastases and metastases in bone and visceral organs.
2011-12-29 | GSE34485 | GEO
Project description:Off-target effect of IACS on breast cancer bone metastases.
| EGAS00001006908 | EGA
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. primary breast tumors vs. bone trephine biopsies
2012-11-09 | E-GEOD-39494 | biostudies-arrayexpress
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.
2012-11-09 | GSE39494 | GEO
Project description:A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at genomic level to identify new therapeutic targets associated with endocrine resistance in the metastatic setting. Identification of chromosomic alterations in bone metastasis derived PDX.
2020-06-29 | GSE149038 | GEO
Project description:Using the immunocompetent bone-metastatic RM1 murine model of prostate cancer, the transriptomes of proliferating (PKH26-) eCFP+/luc2+ RM1 single cells (referred to as RM1536) were compared to dormant (PKH26+) RM1536 single cells dervied from bioluminescence imaging-verified bone metastases in mice at ~d16 post-intracardiac injection of PKH26 labelled RM1536 cells
2020-10-01 | GSE147150 | GEO
Project description:We investigated the role of breast cancer stem-like cells (CSCs-like), isolated from primary tumor, in promoting bone metastases in a human-in-mice model. Luciferase-transduced CD44+CD24- breast CSCs-like were injected through subcutaneous (SC) and intracardiac (IC) route in nonobese/severe combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The implanted bone was viable, active and human neo-vascularization was present. By in vivo luciferase imaging, we monitored tumor growth and detected bone-localized breast CSCs-like, both after SC and IC injection. Bone metastatic lesions were histologically evident, and tumor cells expressed epithelial markers and vimentin. Bone metastatic cells isolated from bone implants showed a CD44-CD24+ phenotype and re-created tumors and bone metastases after injection in secondary mice. A “bone tropism” expression signature was found to distinguish bone-colonizing cells from parental CSCs-like and to persist at subsequent passages also in the absence of surrounding bone tissue. The bone tropism signature displayed significant enrichment in genes discriminating bone metastases of breast cancer from metastases at other organs. Our results demonstrate the ability of breast CSCs-like to promote bone metastasis and provide a CSCs-like bone tropism signature, with potential prognostic value. C10 breast cancer stem-like cells (CSCs-like) were derived as mammospheres from a lobular-infiltrating breast carcinoma (ER+, HER2-). Samples are organized in the following groups: (i) Breast CSCs-like (C10, duplicate); (ii) Luciferase-transduced CSCs-like (C10L, simplicate); (iii) Bone-isolated C10L metastatic cells (C10-bone, duplicate) and subsequently (iv) grown in vitro as spheroids (C10-CSC, simplicate) or (v) re-grown in subcutaneous implants (C10-SC, duplicate).
2013-11-30 | E-GEOD-36102 | biostudies-arrayexpress