Abstract B96: Stimulation of lung adenocarcinoma by social stress

Abstract

Abstract Lung cancer is one of the most common cancers and the leading cause of cancer deaths. Adenocarcinoma (AC) is the leading histological type of lung cancer in all investigated populations and shows a significantly lower association with smoking than other lung cancers. We have previously reported that the proliferation and migration of human AC cells in vitro is stimulated by beta-adrenergic receptors (β-ARs). Agonists for these receptors promoted the progression of AC in hamsters while a beta-blocker had strong cancer preventive effects. The stress neurotransmitters noradrenaline and adrenaline are the physiological agonists for β-ARs. They are released from nerve endings and the adrenal medulla in response to nicotinic acetylcholine receptor (nAChR) stimulation by acetylcholine. Our current study has therefore tested the hypothesis that social stress stimulates the growth of xenografts from human ACs and that nAChRs are involved in this response. Social stress was induced in accordance with published procedures in nude mice carrying xenografts from AC cell lines NCI-H322 and NCI-H441. The diameters of xenografts in mice expose to social stress versus unstressed mice were measured. Levels of noradrenaline and adrenaline, the stress hormone cortisol, the neurotransmitter γ-aminobutyric acid (GABA) in serum and xenograft tissues and levels of cAMP in the cellular fraction of blood and in xenograft tissue were assessed by immunoassays. The levels of GAD65, GAD67, nAChRs and signaling proteins downstream of β-ARs in the tumor tissue were determined by Western blotting. Our data show a significant stimulation of xenograft growth by social stress accompanied by elevated levels of stress neurotransmitters, cortisol and cAMP. In addition, protein expression of nAChR subunits α 3, α4, α5 and α7 as well as β-adrenergic signaling proteins were upregulated while GABA and both GAD enzymes were downregulated. Our data provide first experimental evidence for a significant role of social stress in the development and progression of AC. Supported by Challenge grant 1RC1CA144640-01 with National Institutes of Health. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B96.