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

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. These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. .

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

“…Homing of MSCs involves their survival and directional migration to targeted tissues [32]. Homing to ischemic or damaged tissues is an important feature of MSCs [33]. MSCs can arise from autologous or allogeneic sources.…”

Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro

“…MSC and their progeny may facilitate neoplastic growth (Doron et al, 2018). Communication between MSCs and bone-metastatic DCCs is unclear, but it is possible that MSCs control DCC settlement in the BM as competition for niche space may exist (Dhawan et al, 2016;Gordon et al, 2014;Rossnagl et al, 2018;Shiozawa et al, 2015). Prostate cancer cells induce an osteoblastic-type lesion, while breast cancer and myeloma cells form osteolytic-type of bone lesions (Hashimoto et al, 2018).…”

“…Prostate cancer cells induce an osteoblastic-type lesion, while breast cancer and myeloma cells form osteolytic-type of bone lesions (Hashimoto et al, 2018). Human BM biopsies show higher CD271 + MSCs and CD31 + frequencies in the absence of DCCs in the BM of prostate cancer patients in comparison with breast cancer (Rossnagl et al, 2018). SDF-1 chemokine gradient is one of the most described explanations for tumor-to-BM homing and MSC-derived osteoblasts produce SDF-1, creating a chemo-attractant gradient for CXCR4-expressing cancer cells (Amend et al, 2016;Devignes et al, 2018).…”

Minimal residual disease in prostate cancer patients after primary treatment: theoretical considerations, evidence and possible use in clinical management

“…Recent studies report that CTCs locate to the perivascular niche where endothelial cells, CXCL 12 abundant reticular (CAR) cells and mesenchymal stem cells regulate the implanting tumor cells [75]. Inversely there is a subpopulation of mesenchymal stem cells which carry endothelial and pericyte markers which suppress the homing of CTCs to bone marrow [76]. CPCs home in the niche via a SDF-1 cytokine gradient, SDF-1 is expressed in vascular “hot-spots” corresponding to regions in the bone that attract circulating tumor cells.…”