Second hand smoke stimulates tumor angiogenesis and growth.
Exposure to second hand smoke (SHS) is believed to cause lung cancer. Pathological angiogenesis is a requisite for tumor growth. Lewis lung cancer cells were injected subcutaneously into mice, which were then exposed to sidestream smoke (SHS) or clean room air and administered vehicle, cerivastatin, or mecamylamine. SHS significantly increased tumor size, weight, capillary density, VEGF and MCP-1 levels, and circulating endothelial progenitor cells (EPC). Cerivastatin (an inhibitor of HMG-coA reductase) or mecamylamine (an inhibitor of nicotinic acetylcholine receptors) suppressed the effect of SHS to increase tumor size and capillary density. Cerivastatin reduced MCP-1 levels, whereas mecamylamine reduced VEGF levels and EPC. These studies reveal that SHS promotes tumor angiogenesis and growth. These effects of SHS are associated with increases in plasma VEGF and MCP-1 levels, and EPC, mediated in part by isoprenylation and nicotinic acetylcholine receptors.
Zhu
Bo-qing
BQ
Cardiology Research, VA Medical Center, University of California, San Francisco, CA 94143, USA.
Heeschen
Christopher
C
Sievers
Richard E
RE
Karliner
Joel S
JS
Parmley
William W
WW
Glantz
Stanton A
SA
Cooke
John P
JP
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000209:etiology*; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008464:Mecamylamine / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D009538:Nicotine / Q000633:toxicity*; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018932:Chemokine CCL2; D011725:Pyridines; D011978:Receptors, Nicotinic; D014028:Tobacco Smoke Pollution; D042461:Vascular Endothelial Growth Factor A; D008464:Mecamylamine; D009538:Nicotine; C086276:cerivastatin; D006903:Hydroxymethylglutaryl CoA Reductases