Supplementary-Figure 5 Flow cytometry of MSC markers in human bone marrow biopsies Bone marrow aspirates from patients with prostate cancer (A) and breast cancer (B) who had an evaluation of their bone marrows for the presence of cytokeratin-stained cells to detect disseminated cancer cells (DTCs) were stained for the various MSC markers and analyzed by flow cytometry. The expression of the following markers was not different between cytokeratin negative or positive biopsies: MSCA1, Stro1, CD146, FAP, CD44, CD144, CD73, CD349, CD56 and CD140b in prostate cancer biopsies, n=15/21 (A) and MSCA1, Stro1, CD146, FAP, CD44, CD73 and CD349 in breast cancer biopsies, n=30/30 (B). (C) To exclude any effect of neoadjuvant chemotherapy on the MSC population, the breast cancer patient samples were divided into samples from patients with or without neoadjuvant chemotherapy. Both groups showed an increase in the MSC subpopulation in samples without evidence of cytokeratin-stained cells in bone marrow, n= 10/11/20/19.
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.
