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| 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.
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| 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
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| 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 |
| E-mail(s) |
civitellir@wustl.edu
|
| 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 |
| |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
|
| Samples (22)
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| Relations |
| BioProject |
PRJNA600980 |
| SRA |
SRP241832 |
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