800 | NOVEMBER 2003 | VOLUME 3 www.nature.com/reviews/cancer

H I G H L I G H T S

Despite evidence that it is responsible for ~3,000deaths per year in the United States alone, there is stillsome debate about just how harmful passive smokingreally is. This is due, in part, to a gap in our knowledgeabout the mechanisms by which the inhalation ofenvironmental tobacco smoke (ETS) might causecancer. A study by John Cooke and colleagues nowindicates that ETS promotes tumour growth andangiogenesis, strengthening the link between passivesmoking and cancer.

Cooke and co-workers exposed mice that had beeninjected with lung tumour cells to ETS and studiedthe effects of this on tumour growth andangiogenesis. They saw an increase in tumour growthin these mice that was five times greater than that inunexposed animals. The exposed mice also showed anincrease in tumour blood-vessel density that wasdouble that seen in control mice, indicating thatcomponents of ETS promote angiogenesis.

Nicotine is one of the main components of ETS and,although it is only a weak carcinogen, there isevidence that it can promote tumour developmentthrough indirect mechanisms. It has recently beenshown that nicotine can induce angiogenesis byactivating nicotinic acetylcholine receptors (nAchRs)on the surface of endothelial cells, which stimulatestheir proliferation and the subsequent formation ofblood vessels. To test whether increases in tumoursize and angiogenesis in mice exposed to ETS weredue to the effects of nicotine, Cooke and colleaguestested whether this effect could be blocked bymecamylamine, an inhibitor of nAchRs. Whenexposed mice were treated with this drug, theformation of new blood vessels was almostcompletely abolished, indicating that nicotine has akey role in the induction of angiogenesis by ETS.

The authors also investigated the effect of ETS on thelevels of two other angiogenesis promoters, monocytechemoattractant protein 1 (Mcp1) and vascularendothelial growth factor (Vegf). Increased levels ofboth of these proteins were found in serum fromexposed mice. Mecamylamine blocked the increase inVegf levels by approximately two-thirds, indicatingthat nicotine induces angiogenesis through Vegfsignalling as well as by having a direct effect onendothelial cells. However, mecamylamine had littleeffect on Mcp1 levels, indicating that other compoundsthat are present in ETS in addition to nicotine canstimulate angiogenesis.

Statins — which are best known for their use intreating high cholesterol levels — are potentialangiogenesis inhibitors as they inhibit the secretion ofMcp1 and interfere with signalling downstream of theVegf receptor. Cooke and colleagues tested the effect ofone of these molecules, cerivastatin, on tumourdevelopment in mice that were exposed to ETS.

Cerivastatin substantially blocked the increases inboth tumour size and angiogenesis in these mice,indicating a possible method of counteracting theharmful effects of inhaling this type of smoke.

Interestingly, the effects of ETS described hereindicate a role for nicotine in promoting the growthof existing tumours rather than in initiating tumourformation. This indicates that it acts in concert withother more strongly carcinogenic ETS componentsto exert its harmful effects. The authors estimate thatthe levels of nicotine and other toxic chemicals thatare present in the ETS used in these experimentswere similar to those that are encountered by peoplein smoky environments such as bars and casinos.This study therefore provides compelling evidencethat passive smoking can stimulate tumour growthand that it does indeed pose a serious threat tohuman health.

Louisa Flintoft

References and linksORIGINAL RESEARCH PAPER Zhu, B. et al. Second hand smokestimulates tumor angiogenesis and growth. Cancer Cell 4, 191–196 (2003)FURTHER READING Hecht, S. S. Tobacco carcinogens, their biomarkersand tobacco-induced cancer. Nature Rev. Cancer 4, 733–744 (2003)WEB SITEJohn Cooke’s lab:http://cardiology.stanford.edu/VascularMedicine/endothelial_biology.htm

Inhaling can seriously damage your health

C A R C I N O G E N E S I S

Risky businessSun bathing could be aneven more dangeroushobby than haspreviously been thought,as new researchindicates that sunscreenlotions might noteffectively protectagainst skin cancer.

Professor Roy Sandersand colleagues — from theresearch charity Raft,based at the MountVernon hospital in London,UK — exposed skin thatwas removed fromconsenting patients toultraviolet A (UVA) light atlevels similar to thosefound in sunlight. Theythen compared the effectsof applying three differentbrands of high-factorsunscreen lotion. Althoughthe sunscreen preventedthe skin from burning —attributed to anothercomponent of sunlight,UVB — the UVA could stillpenetrate the skin, leadingto release of free radicals,which can cause DNAdamage and lead to theformation of malignantmelanoma.

Roy Sanders said that“This is a problembecause if people areusing these creams onthe supposition that theydo offer protection thenthey might be puttingthemselves at higher riskof skin cancer” (BBCNews Online, 29September 2003). Thesun protection factor(SPF) of sun lotion refersonly to protection fromUVB, so using sunscreenmight actually beharmful, as it encouragespeople to stay in the sunfor longer.

The sunscreenmanufacturers Boots havefought back though, asthey claim that theirproducts are important forsun protection, as“staying out of thesunshine completely isnot an option most peoplecare for” (TheIndependent, 29September 2003).

Emma Greenwood

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