Neoangiogenesis, lymphangiogenesis and neoneurogenesis are being considered to occur in concert and synergistically

orchestrate the development, progression and responsiveness to the prevention and therapy of tumours [4] and [5]. Experimental and clinical evidences this website also show that some cancers are innervated by nerve fibres and form neuro-neoplastic synapses which directly secret neurotransmitters to act on the cancer cells [6] and [7]. Cancer cells not only express receptors of neurotransmitters but also are able to synthesize several different neurotransmitters [3] and [8]. Some of them could act locally in an autocrine and paracrine manners or systemically circulate and be back to tumour cells to conduct relevant regulation on these cells. β-Adrenergic system consists of catecholamines PI3K Inhibitor Library concentration and their respective receptors including α- and β-adrenergic receptors which are widely expressed in most of the mammalian tissues. Adrenaline and noradrenaline are classic neurotransmitters mediating fight-to-flight stress responses via sympatho-adrenomedullary system [9] and [10]. Noradrenaline is released primarily from the sympathetic

nerves and adrenaline is secreted mainly by the adrenal medulla. Their release and secretion are triggered by stimulation of the nicotinic/acetylcholine system in the central and peripheral sympathetic nervous systems and in the adrenal medulla (Fig. 1). Recent studies further disclose that some cancer cells contain all the enzymes for the

adrenaline synthesis and are capable to secrete adrenaline after stimulation, aminophylline for example by nicotine [11], [12] and [13]. Adrenaline and noradrenaline could bind to β-adrenoceptors with different affinities. Adrenaline preferentially binds to β2-adrenoceptors whereas noradrenaline shows higher affinity to β1-receptors [14]. Recently, a growing number of studies suggest that biobehavioural factors especially various stress-related persistent stimulations might accelerate cancer progression, which is mainly contributed by β-adrenergic system activation (Fig. 1) [15], [16] and [17]. In this review, we will focus on the influences of β-adrenergic system on several crucial steps in cancer development and progression, and further discuss the potential applications of β-blockers in cancer treatment. The roles of β-adrenergic system in cancer development and progression almost involve in every hallmarks of cancer development described above. The influences of β-adrenergic system on energy metabolism and immune system have been shown to regulate cancer metastasis [8], [18], [19] and [20]. But here we focus on the discussion on the common tumorigenic pathways during tumour progression.