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Figure S1 from A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow

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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
<p>Supplementary-Figure 1 Tumor cell infiltration of other organs after PTH/ZA treatment (A) The combined treatment with PTH/ZA does not affect the homing of MDA tumor cells to other organs; n=14/15 in 2 experiments. Evaluation of blood vessel numbers and binding of cancer cells to vascular cells after PTH/ZA treatment (B) PTH/ZA did not affect blood vessel numbers in the treated mice. Proximal tibiae from 4 mice/group were evaluated and the number of blood vessels adjusted to the evaluated area. (C) Binding of cancer cells to immune cells (CD45+) or vascular cells (CD31 or PLVAP) was not affected by treatment with PTH/ZA, n=13/11. Bone marrow from control and treated mice that received cancer cells 24 hours prior to bone marrow isolation was subjected to addition of magnetic beads precoated with CD45 antibody and carefully removed. Addition of either CD31 or PLVAP antibody coated beads followed and beads were used for DNA isolation and evaluation of cancer cell presence. The amount of cancer cell specific DNA was corrected to murine -actin. PTH/ZA treatment does not affect colony forming units of hematopoietic populations (D) There were no changes in various progenitor colonies when bone marrow from treated mice was cultured in vitro for 2 weeks in specialized media, stained with crystal violet and counted; n=6/6/6/6 in 3 experiments. CFU-GEMM is shown in Fig. 1C. Examples of the various colonies are shown below the graphs (light microscopy, 40x).</p>

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Max-Planck Society

German Research Council-DFG

German Academic Exchange Service-DAAD

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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.