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. Author manuscript; available in PMC: 2019 Oct 1.
Published in final edited form as: Curr Osteoporos Rep. 2018 Oct;16(5):596–602. doi: 10.1007/s11914-018-0471-7

Figure 1. The roles of the interactions between bone marrow resident disseminated tumor cells (DTCs) and bone marrow stroma in cancer cell dormancy and recurrence.

Figure 1.

Left Panel: Mesenchymal stem cells (MSCs) are mobilized to DTCs through CXC-chemokine ligand 12 (CXCL12) and release exosomes containing dormancy promoting miRNA or are cannibalized by the DTCs. Inactive endothelial cells release thrombospondin 1 (TSP1) to promote dormancy and reduce proliferation of DTCs. Osteoblasts secrete transforming growth factor (TGF)-β2 and growth differentiation factor 10 (GDF10) to inhibit cellular proliferation, and express leukemia inhibitory factor (LIF) that is recognized by LIF receptor (LIFR) on dormant DTCs.

Right Panel: DTCs express interferon-γ (IFN- γ) that inhibits TSP1 expression in endothelial cells. Active endothelial cells secrete TGF-β1 and periostin to promote DTC proliferation. DTCs secrete vascular cell adhesion protein 1 (VCAM1) to promote maturation and activation of osteoclasts. Graphics adapted from Servier Medical Art (https://smart.servier.com/).