Nicotine, lung and cancer.
The respiratory epithelium expresses the cholinergic system including nicotinic receptors (nAChRs). It was reported that normal human bronchial epithelial cells (BEC), which are the precursor for squamous cell carcinomas, and small airway epithelial cells (SAEC), which are the precursor for adenocarcinomas, have slightly different repertoires of nAChRs. Studies shown that nAChRs expressed on lung carcinoma or mesothelioma form a part of an autocrine-proliferative network facilitating the growth of neoplastic cells; others demonstrated that nicotine can promote the growth of colon, gastric, and lung cancers. Nicotine and structurally related carcinogens like NNK [4-(methylnitrosoamino)- 1-(3-pyridyl)-1-butanone] and NNN (N'-nitrosonornicotine) could induce the proliferation of a variety of small cell lung carcinoma cell lines and endothelial cells and nicotine in non-neuronal tissues -including lung- induces the secretion of growth factors (bFGF, TGF-alpha, VEGF and PDGF), up regulation of the calpain family proteins, COX-2 and VEGFR-2, causing the eventual activation of Raf/MAPK kinase/ERK (Raf/MEK/ERK) pathway contributing to the growth and progression of tumors exposed to nicotine through tobacco smoke or cigarette substitutes. It has been demonstrated that nicotine promotes the growth of solid tumors in vivo, suggesting that might induce the progression of tumors already initiated. While tobacco carcinogens can initiate and promote tumorigenesis, the exposure to nicotine could confer a proliferative advantage to early tumors but there is no evidence that nicotine itself provokes cancer. This is supported by the findings that nicotine can prevent apoptosis induced by various agents - such as chemotherapeutic in NSCLC, conferring a survival advantage as well.
Grozio
Alessia
A
Translational Research B (Lung Cancer), Department of Integrated Medical Oncology (DOMI), National Cancer Institute, Largo Rosanna Benzi 10, Genoa, Italy. alessia.grozio@libero.it
Catassi
Alessia
A
Cavalieri
Zita
Z
Paleari
Laura
L
Cesario
Alfredo
A
Russo
Patrizia
P
D000818:Animals; D001980:Bronchi / Q000166:cytology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D008954:Models, Biological; D008956:Models, Chemical; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009538:Nicotine / Q000009:adverse effects*; D011978:Receptors, Nicotinic / Q000378:metabolism
D011978:Receptors, Nicotinic; D009538:Nicotine