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posted on 2023-03-31, 01:22 authored by Stephanie Rossnagl, Hiba Ghura, Christopher Groth, Eva Altrock, Franz Jakob, Sarah Schott, Pauline Wimberger, Theresa Link, Jan Dominik Kuhlmann, Arnulf Stenzl, Jörg Hennenlotter, Tilmann Todenhöfer, Markus Rojewski, Karen Bieback, Inaam A. Nakchbandi Supplementary-Figure 2 Characterization of the affected stromal population after PTH/ZA treatment (A-B) Using flow cytometry, potential markers of mesenchymal stromal cells were evaluated in bone marrow of PTH/ZA-treated mice. Gating was applied after the exclusion of hematopoietic and erythroid cells (CD45- Ter119-). (B) PTH/ZA diminished the size of populations expressing the following surface markers: Sca1+, CD29+, CD31+, CD44-, αSMA+, leptin receptor+, and CD146+; n=15/15 in 3 experiments.
Funding
Max-Planck Society
German Research Council-DFG
German Academic Exchange Service-DAAD
History
ARTICLE ABSTRACT
Breast and prostate cancer cells home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. We characterize here the elusive premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in cancer cell homing. Decreasing the number of MSC pharmacologically enhanced cancer cell homing to the bone marrow in mice. In contrast, increasing the number of these MSCs by various interventions including G-CSF administration diminished cancer cell homing. The MSC subpopulation that correlated best with cancer cells expressed stem, endothelial, and pericytic cell markers, suggesting these cells represent an undifferentiated component of the niche with vascular commitment. In humans, a MSC subpopulation carrying markers for endothelial and pericytic cells was lower in the presence of cytokeratin+ cells in bone marrow. Taken together, our data show that a subpopulation of MSC with both endothelial and pericytic cell surface markers suppresses the homing of cancer cells to the bone marrow. Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC subpopulation could prove useful in determining the risk of metastatic disease, and its manipulation might offer a new possibility for diminishing bone metastasis formation.Significance: These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. Cancer Res; 78(1); 129–42. ©2017 AACR.
