Autocrine Motility Factor Possesses a Possibility of Developing a New Target for Anti-Cancer Treatment

Tatsuyoshi      Funasaka; Takashi      Yanagawa; Victor      Hogan; Avraham      Raz

Abstract

Autocrine motility factor (AMF) is a type of tumor-secreted cytokine stimulating cell motility via AMF receptor (AMFR)-mediated signaling pathways. There are many reports that enhanced AMF levels and AMFR overexpressions are correlated with the tumor progression and its malignancy. It is thought previously that AMF is a tumor-specific factor functioning in an autocrine manner, however, recent studies show that tumor-secreted AMF stimulates normal cell motility in a paracrine manner, and promotes angiogenesis and other pathological phenomena. AMF is also involved with vascular endothelial growth factor (VEGF), which is the most important tumor angiogenic and mitogenic factor. Hypoxia-induced AMF is regulated by VEGF, furthermore, the signaling of AMF-AMFR in host endothelial cells induces expression of a VEGF receptor Flt- 1. This malignant cycle comprising of Flt-1, VEGF and AMFR will result in marked locomotive, angiogenic and further metastatic synergy. Experimental treatment with AMF inhibitors succeeded in reducing tumorinduced angiogenesis and accumulation of ascites fluid, which renders AMF to the target molecule. It is further suggested that AMF brings anti-apoptotic ability to the tumor cell itself to gain a resistance against anticancer drugs. AMF inhibitors could support the anti-cancer drugs due to its ability to lead the tumor cells to cell death. This article reports that AMF is a significant factor associated with the development of tumors, and it will be a new target for anti-cancer treatment.

Keywords: amf, cell motility, angiogenesis, ascites fluid, flt, apoptosis

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