Bone marrow mesenchymal stem cells increase motility of prostate cancer cells via production of stromal cell‐derived factor‐1α

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.

The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

“…32 Furthermore, nutrient stress has also been implicated in enhancing cancer stem cell phenotype through Wnt signaling, 33,34 and stromal cells were found to mediate cancer cell adhesion and motility. [35][36][37] Thus, there is a bi-directional effect of the tumor microenvironment in which the environment affects the tumor cell characteristics and in return the tumor cells remodel their microenvironment. In particular, it is believed that CSCs are especially efficient in modulating their microenvironment.…”

Zoledronic Acid and Leuprorelin Acetate, Alone or in Combination, Similarly Reduce Proliferation and Migration of Prostate Cancer Cells In Vitro

“…We previously demonstrated that BM-MSCs isolated with this procedure are CD90 + and CD34/CD45 -and that under opportune stimuli they can differentiate [7,25]. We also previously reported that BM-MSCs stimulate PCa cell migration [22]. BM-MSCs were therefore included in the present study according to the described protocols.…”

“…After 6 h incubation, cells were collected and treated as detailed by Mognetti et al [22] and immunoblotted according to Penna et al [24]. In parallel proliferation tests-as previously described-performed in the same culture conditions in order to exclude any confounding element, no significant cytotoxicity was appreciable at the chosen concentration after 6 h incubation.…”

“…BM-MSC conditioned medium was collected after three days of culture, centrifuged to eliminate cells and cellular debris, and freshly used or frozen [22].…”

“…Bone metastases likely depend on crosstalk between metastatic cells, bone matrix, osteoblasts and osteoclasts, and cellular components of the bone marrow microenvironment. Among these, bone marrow mesenchymal stem cells (BM-MSCs) play a paramount role in the so-called metastatic niche [14,22]. In particular, BM-MSC paracrine factors may allow tumor cells to access cellular niches favoring tumor cell survival and growth [14,22].…”