Abstract

Adrenomedullin (AM) is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

Highlights

  • Adrenomedullin (AM) is a 52 amino acid peptide originally isolated from a human pheochromocytoma [1] that bears multifactorial regulatory properties ranging from inducing vasodilatation to modulating cellular growth [2]

  • TRPV2 expression in bladder is shown to correlate with the grade and stage of cancer [14] but nothing is known about its potential role in bladder cancer cell migration/ invasion

  • In the present work we investigated the involvement of TRPV2 in the effect of AM on the multistep process of invasion in two highly invasive cell lines: the PCa (Prostate Cancer) cells PC-3 and the UC (Urothelial Carcinoma) cells T24/83

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Summary

Introduction

Adrenomedullin (AM) is a 52 amino acid peptide originally isolated from a human pheochromocytoma [1] that bears multifactorial regulatory properties ranging from inducing vasodilatation to modulating cellular growth [2]. In non-excitable cells, Ca2+ entry is provided by ion channels that are activated by various chemical and physical stimuli. Some of these Ca2+ entry channels are members of the ‘‘transient receptor potential’’ (TRP) family of cationic channels [8]. Recent studies from our laboratory have shown show that TRPV2 is expressed in the more aggressive prostate cancer cells and stimulates the migration and invasive phenotype of these cells [12,13]. TRPV2 expression in bladder is shown to correlate with the grade and stage of cancer [14] but nothing is known about its potential role in bladder cancer cell migration/ invasion

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