Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and two of the three melanocyte cell lines examined. Epo expression was significantly higher in melanoma than in benign nevi as determined by immunohistochemistry. Although melanoma cells secreted Epo in normoxic condition in vitro, hypoxia and CoCl(2) treatment increased Epo secretion. EpoR in melanoma cells was functional, because exogenous Epo increased melanoma resistance to hypoxic stress, pretreatment of melanoma cells with Epo significantly increased resistance to dacarbazine treatment, and Epo increased the phosphorylation of EpoR, RAF, and MEK. In conclusion, we demonstrated constitutive expression of Epo and EpoR as well as autonomous secretion of Epo by melanoma cells, indicating a novel autocrine loop of Epo in melanoma. The results suggest that the autocrine and paracrine functions of Epo might play a role in malignant transformation of melanocytes and in the survival of melanoma cells in hypoxia and other adverse conditions.

How to deliver chemotherapeutic drugs efficiently and selectively to tumor cells to improve therapeutic efficacy remains a difficult problem. We herein construct an efficient cell-targeting drug delivery system (Sgc8-MSN/Dox) based on aptamer-modified mesoporous silica nanoparticles that relies on the tumor-targeting ability of the aptamer Sgc8 to deliver doxorubicin (Dox) to leukemia cells in a targeted way, thereby improving therapeutic efficacy and reducing toxicity. In this work, Sgc8-MSN/Dox showed sustained Dox release, and they targeted and efficiently killed CCRF-CEM human acute T lymphocyte leukemia cells, suggesting potential as a cancer therapy.

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