Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells

Abstract

Zoledronic Acid (ZA) rapidly concentrates into the bone and reduces skeletal-related events and pain in bone metastatic prostate cancer (PCa), but exerts only a limited or absent impact as anti-cancer activity. Recently, we developed self-assembling nanoparticles (NPS) encapsulating zoledronic acid (NZ) that allowed a higher intratumor delivery of the drug compared with free zoledronic acid (ZA) in in vivo cancer models of PCa. Increasing evidence suggests that Bone Marrow (BM) Mesenchymal stromal cells (BM-MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis.We demonstrated that treatment with NZ decreased migration and differentiation into adipocytes and osteoblasts of MSCs and inhibited osteoclastogenesis. Treatment with NZ reduced the capability of MSCs to promote the migration and the clonogenic growth of the prostate cancer cell lines PC3 and DU145. The levels of Interleukin-6 and of the pro-angiogenic factors VEGF and FGF-2 were significantly reduced in MSC-CM derived from MSCs treated with NZ, and CCL5 secretion was almost totally abolished. Moreover, treatment of MSCs with supernatants from PC3 cells, leading to tumor-educated MSCs (TE-MSCs), increased the secretion of IL-6, CCL5, VEGF and FGF-2 by MSCs and increased their capability to increase PC3 cells clonogenic growth. Treatment with NZ decreased cytokine secretion and the pro-tumorigenic effects also of TE-MSCS. In conclusion, demonstrating that NZ is capable to inhibit the cross talk between MSCs and PCa, this study provides a novel insight to explain the powerful anticancer activity of NZ on PCa.

Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

“…Breast cancer cells stimulated de novo secretion of the chemokine CCL5 from mesenchymal stem cells, which then acted in a paracrine fashion on the cancer cells to enhance their motility, invasion, and metastasis [ 71 ]. Zoledronic acid (ZA) [ 72 ], as well as PEGylated nanoparticles (NPs) encapsulating ZA [ 73 ], decreased both CCL5 and IL-6 secretion by MSCs, suggesting that ZA may exert antitumor activity by affecting the ability of MSCs to interact with breast cancer cells.…”

The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?

“…Moreover, evidence that seems to show an increased risk for acute prostatitis rather than for chronic prostatitis, is influenced by the same potential detection bias. Different cancer types (i.e., lung cancer, pancreatic cancer, glioblastoma, meningioma, myeloma, and myeloma) are characterized by distinct patterns revealed by corona composition, constituting a "fingerprint" for each cancer type [51][52][53][54].…”

Selection of Angiogenic Markers that Predict the Transition from Bisphosphonate Exposure to MRONJ in a Rat Model

“…FGF2 also appears to increase expression of the tissue factor F3 through EGFR1 (20). The effects of this pathway were likely reversed through the addition of zolendronic acid, which has been shown to reduce FGF2 expression (21), while increasing expression of Thbs1 (22).…”