Infiltrating bone marrow mesenchymal stem cells increase prostate cancer stem cell population and metastatic ability via secreting cytokines to suppress androgen receptor signaling

Abstract

Although the contribution of the bone marrow mesenchymal stem cells (BM-MSCs) in cancer progression is emerging, their potential roles in prostate cancer (PCa) remain unclear. Here, we showed that PCa cells could recruit BM-MSCs and consequently the metastatic ability of PCa cells was increased. We also found that the increased metastatic ability of PCa cells could be due to the increased PCa stem cell population. Mechanism dissection studies found that the upregulation of Chemokine ligand 5 (CCL5) expression in BM-MSCs and PCa cells, after MSCs infiltrated into the PCa cells, subsequently downregulated androgen receptor (AR) signaling, which was due to inhibition of AR nuclear translocation. Interruption of such signaling led to suppression of the BM-MSCs-induced PCa stem cell population increase and thereby inhibited the metastatic ability of PCa cells. The PCa stem cell increase then led to the upregulation of matrix metalloproteinase 9, ZEB-1, CD133 and CXCR4 molecules, and enhanced the metastatic ability of PCa cells. Therefore, we conclude that the BM-MSCs-mediated increased metastatic ability of PCa cells can be due to the PCa stem cell increase via alteration of the CCL5-AR signaling pathway. Together, these results uncover the important roles of BM-MSCs as key components in the prostate tumor microenvironment to promote PCa metastasis and may provide a new potential target to suppress PCa metastasis by blocking BM-MSCs infiltration into PCa.

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

“…Furthermore, these findings are substantiated by a previous work demonstrating enhanced tumor cell growth by MSC [34][35][36][37], although there are also controversial studies suggesting a reduced tumor cell proliferation in the presence of MSC [38,39]. The divergent effects of MSC on tumor cells may be caused, in part, by a different activation status within the heterogeneous MSC population involving interference with the b-catenin pathway such as DKK-1-mediated depression of Wnt signaling [40].…”

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

“…24 Prostate CSCs also participate in bone metastasis, castration resistance, radiotherapy resistance, and other types of cancer developmental progressions. [25][26][27] Therefore, it is important for us to identify new drugs that can target prostate CSCs or attenuate the stemness of prostate cancer cells.…”

CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment

“…Recently, BM microenvironment has become a research focus in cancer research. Cancer cells affected by BM microenvironment are more likely to develop malignant characteristics such as metastasis, 25 angiogenesis, 26 and drug resistance. 27 BMSCs derived from BM tissue is abundant in the tissues adjacent to OS.…”