RESUMEN
BACKGROUND: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and aggressiveness. METHODS: A PI3K inhibitor, Bevacizumab (an anti-VEGF-A antibody), and an anti-FGF2 antibody were added to the EPCs' conditioned medium (EPC-CM), and their impacts on OS cell (U2-OS and 143B) proliferation, migration, invasion, MMP9 expression, and AKT phosphorylation were determined. The autocrine role of VEGF-A was assessed using Bevacizumab treatment and VEGF-A silencing in OS cells. Toward this end, an orthotopic mouse OS model was established. Mouse and human tumors were immunolabeled with antibodies to the abovementioned factors. RESULTS: EPC-CM enhanced osteosarcoma MMP9 expression, invasiveness, and migration via the PI3K/AKT pathway. The addition of Bevacizumab and an anti-FGF2 antibody to the EPC-CM diminished OS cell migration. The autocrine role of VEGF-A was assessed using Bevacizumab and VEGF-A silencing in OS cells, resulting in decreased AKT phosphorylation and, consequently, diminished invasiveness and migration. Consistently, OS xenografts in mice displayed high VEGF-A and FGF2 levels. Remarkably, lung metastasis specimens derived from OS patients exhibited marked immunolabeling of CD31, VEGF-A, and FGF2. Conclusions: EPCs promote OS progression not only by physically incorporating into blood vessels, but also by secreting cytokines, which act via paracrine signaling. EPCs induced in vitro MMP9 overexpression, invasion, and migration. Additional animal studies are warranted to further expand these results. These findings may pave the way toward the development of novel EPCs-targeted therapeutics aimed at blocking OS metastasis.
RESUMEN
Adjuvant chemotherapy is recommended in high-risk stage II-III colorectal cancer (CC). We examine the effect of daily wheatgrass juice (WGJ) intake in addition to chemotherapy on immune parameters, including IL-6, IL-8, IL-10, IL-12, and white blood cells (WBCs) among CC patients. In a controlled prospective trial, 100 stage II-III CC patients were enrolled. According to patient preference, they were divided into two subgroups, control group and intervention group, 50 patients each, all of whom received the same standard postoperative adjuvant chemotherapy, plus consumption of 60 cc WGJ daily in the intervention group. Blood samples were collected at baseline (T0) and upon treatment termination, 5-6 months later (T1). Cytokine concentrations were assessed using ELISA kits. Anti-inflammatory cytokine IL-10 concentrations were significantly higher in the WGJ group than in the control group at T1. The decline in WBC counts between T0 and T1 was significantly lower in the WGJ group. No significant differences were observed in IL-6, IL-8, and IL-12 concentrations between the study groups. The higher levels of IL-10 and the attenuating of WBC decline during chemotherapy may constitute preliminary evidence of the beneficial effects of WGJ on immune parameters, when given as a supplement to standard care. In light of these preliminary results, WGJ supports immunological parameters during adjuvant chemotherapy. Nevertheless, future studies are needed in order to translate those results to clinical recommendations for cancer survivors.