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Series GSE143586 Query DataSets for GSE143586
Status Public on Aug 13, 2020
Title Ectopic Osx+ Cells Affect Tumor Growth
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell-cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular “dock” for disseminated tumor cells to establish pre-metastatic niches within the bone. Contrary to expectations, the breast cancer cells were able to form tumors in bone and to induce osteolysis in Cdh2-cKO as well as in control mice. Notably, subcutaneous tumors grew larger in Cdh2-cKO relative to control littermates. Cell tracking experiments using the Ai9 reporter revealed the presence of Osx+ and Ncad+ cells in the stroma of extra-skeletal tumors and in a small population of lung cells, a frequent site of breast cancer metastasis. Gene expression analysis by RNAseq of CD45- Osx+ cells isolated from extra-skeletal tumors revealed alterations of pro-tumorigenic signaling pathways in Cdh2-cKO cells relative to control Osx+ cells. Also surprisingly, we find Osx+ cells present in the circulation, and the majority of tumor-associated and circulating Osx+ cells express the hematopoietic marker CD45, have a phenotypic profile resembling that of tumor infiltrating myeloid and lymphoid populations, but with higher expression of lymphocytic immune suppressive genes. Our results indicate that Osx marks distinct tumor promoting CD45- and CD45+ populations and challenge the dogma that osteogenic and hematopoietic markers are mutually exclusive. They also show that Ncad in CD45- Osx+ cells is not necessary for the establishment of bone metastases, but in extra-skeletal tumors it regulates pro-tumorigenic support by the microenvironment.
Overall design Profiling mRNA expression in Osx+ cells (CD45+ and CD45-) isolated from the stromal component of subcutaneous tumors grown in Cdh2-cKO and wild type mice
Contributor(s) Civitelli R, Faccio R, Fontana F, Ricci B
Citation(s) 32755539, 33912383
Submission date Jan 13, 2020
Last update date May 06, 2021
Contact name Roberto Civitelli
Phone 3144548408
Organization name Washington University St. Louis
Department Bone and Mineral Diseases
Lab CB 8301
Street address 660 S. Euclid Ave.
City St. Louis
State/province Missouri
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (22)
GSM4263468 Osx+ CD45- WT rep1
GSM4263469 Osx+ CD45- WT rep2
GSM4263470 Osx+ CD45+ WT rep1
BioProject PRJNA600980
SRA SRP241832

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Supplementary file Size Download File type/resource
GSE143586_RAW.tar 57.5 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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