Recently, it has been described that programmed cell death protein 1 (PD-1) overexpressing melanoma cells are highly aggressive.,However, until now it has not been defined which factors lead to the generation of PD-1 overexpressing subpopulations.,Here, we present that melanoma-derived exosomes, conveying oncogenic molecular reprogramming, induce the formation of a melanoma-like, PD-1 overexpressing cell population (mMSCPD-1+) from naïve mesenchymal stem cells (MSCs).,Exosomes and mMSCPD-1+ cells induce tumor progression and expression of oncogenic factors in vivo.,Finally, we revealed a characteristic, tumorigenic signaling network combining the upregulated molecules (e.g., PD-1, MET, RAF1, BCL2, MTOR) and their upstream exosomal regulating proteins and miRNAs.,Our study highlights the complexity of exosomal communication during tumor progression and contributes to the detailed understanding of metastatic processes.
To investigate the feasibility of using bevacizumab to improve the survival of American Joint Committee on Cancer (AJCC) stage III melanoma patients, we investigated how a single bevacizumab treatment affected nodal disease and a panel of biomarkers in clinically fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT)-staged, stage III melanoma patients, prior to therapeutic lymph node dissection (TLND).,Four weeks before TLND, nine patients (median age 50, range 28.8-62.1 years; two male, seven female) with palpable lymph node metastases received 7.5 mg/kg bevacizumab.,Before and after this treatment, all patients were assessed by measurements of the maximum standardized uptake value (SUVmax) by FDG-PET scan, and serum S-100B and lactate dehydrogenase (LDH).,After TLND, the dissection specimen was analyzed for number of removed lymph nodes, number of metastatic lymph nodes, and tumor necrosis.,Median follow-up was 15.5 (2.2-32.9) months.,Histopathological analysis revealed tumor necrosis in six patients, of whom five had an S-100B decline and one had an unchanged S-100B level after bevacizumab.,The other three patients showed an S-100B increase and no necrosis.,Tumor necrosis was correlated with S-100B decrease (P = 0.048).,No association was found between necrosis and the markers SUVmax and LDH.,No wound healing disturbances were encountered.,Tumor necrosis in dissection specimens was associated with declining S-100B levels, while elevated S-100B was only found in cases with no necrosis.,Bevacizumab might be useful in treating AJCC stage III melanoma patients prior to TLND, and S100-B appears to be a useful marker for assessment of treatment effects.