Abstract
Prostate cancer frequently metastasizes to the bone, and the interaction between cancer cells and bone microenvironment has proven to be crucial in the establishment of new metastases. Bone marrow mesenchymal stem cells (BM-MSCs) secrete various cytokines that can regulate the behaviour of neighbouring cell. However, little is known about the role of BM-MSCs in influencing the migration and the invasion of prostate cancer cells. We hypothesize that the stromal cell-derived factor-1α released by BM-MSCs may play a pivotal role in these processes. To study the interaction between factors secreted by BM-MSCs and prostate cancer cells we established an in vitro model of transwell co-culture of BM-MSCs and prostate cancer cells DU145. Using this model, we have shown that BM-MSCs produce soluble factors which increase the motility of prostate cancer cells DU145. Neutralization of stromal cell-derived factor-1α (SDF1α) via a blocking antibody significantly limits the chemoattractive effect of bone marrow MSCs. Moreover, soluble factors produced by BM-MSCs greatly activate prosurvival kinases, namely AKT and ERK 1/2. We provide further evidence that SDF1α is involved in the interaction between prostate cancer cells and BM-MSCs. Such interaction may play an important role in the migration and the invasion of prostate cancer cells within bone.
Highlights
Prostate cancer is the second leading type of cancer in men in industrialized countries
Several lines of evidence suggest that the stromal cell-derived factor-1a (SDF1a)/CXCR4 axis is involved in tumour progression and the development of distant metastases; this aspect has been highlighted for breast carcinoma [13,14,15], which is characterized by the frequent appearance of bone metastasis
We suggested that Bone marrow mesenchymal stem cells (BM-mesenchymal stem cells (MSCs)) production of soluble factors and SDF1a/CXCR4 interaction are crucial for attracting prostate tumour cells to the bone marrow niche
Summary
Prostate cancer is the second leading type of cancer in men in industrialized countries. It is known that multiple factors, including the chemotactic responses to bone-derived factors and the interaction of prostate cancer cells with the bone microenvironment, are of paramount importance [1]. CXCR4 overexpression is known in more than 20 human tumour types, including ovarian [8], prostate [9], esophageal [10], melanoma [11], neuroblastoma [12]. Several lines of evidence suggest that the SDF1a/CXCR4 axis is involved in tumour progression and the development of distant metastases; this aspect has been highlighted for breast carcinoma [13,14,15], which is characterized by the frequent appearance of bone metastasis.
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