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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 3 Correlations between MSCs, CFU-f and homing (A) The percentage of detected MSCs in vivo in control mice and after PTH/ZA treatment correlates negatively with the number of detected tumor cells in the bone marrow, n=40, Pearson''s correlation r=-0.59. (B) The percentage of detected MSCs in vivo in control mice and after PTH/ZA treatment correlates positively with the number of CFU-fs in vitro. (n=27; Pearson correlation r=0.57). (C) In the absence of tumor cells, the combination of PTH/ZA diminishes the MSC subpopulation. Please compare to Fig. 1G obtained in the presence of cancer cells, n=9/12/9/9 in three experiments. Apoptosis after PTH/ZA treatment (D) Apoptosis in CD45- Ter119- CD31+ cells increased after treatment with PTH/ZA and ZA alone, whereas apoptosis in CD45- Ter119- CD146+ cells only increased in the PTH/ZA-treated group, n=10/12/7/7 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.
