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.
Subject(s)
Chemokine CCL5/genetics , Mesenchymal Stem Cells/metabolism , Neoplastic Stem Cells/metabolism , Prostatic Neoplasms/pathology , Receptors, Androgen/metabolism , AC133 Antigen , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Bone Marrow Cells/metabolism , Cell Line, Tumor , Chemokine CCL5/metabolism , Coculture Techniques , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , Glycoproteins/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Lymphatic Metastasis , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Nude , Neoplasm Transplantation , Peptides/genetics , Peptides/metabolism , Prostatic Neoplasms/metabolism , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Microenvironment , Up-Regulation , Zinc Finger E-box-Binding Homeobox 1ABSTRACT
A bioflocculant from a fungus, Aspergillus sp. JS-42, was purified by precipitations with acetone and cetylpyridinium chloride. The flocculating activity was not significantly affected by pH from 3 to 8, but was stimulated by the addition of CaCl2, and was effective only when the reaction mixture contained an adequate amount of flocculant. The flocculant could efficiently flocculate all tested solids suspended in aqueous solution, including various microorganisms, organic acids, and inorganic materials.
