Overexpression of SLURP-1 and -2 alleviates the tumorigenic action of tobacco-derived nitrosamine on immortalized oral epithelial cells.
Recent research has demonstrated that mucocutaneous epithelial cells express functional nicotinic acetylcholine receptors (nAChRs) and that tobacco-derived carcinogenic nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein)-1 and -2 can act as non-canonical ligands of these receptors. It was found that recombinant SLURP-1 and -2 can lessen tumorigenic activity of nitrosamines. The immortalized esophageal keratinocytes (Het-1A cells) exhibit low SLURP-1 and -2 mRNA levels that decrease further after treatment with NNK. Based on these observations, we hypothesized that overexpression of full length SLURP proteins may protect Het-1A cells from malignant transformation by NNK. The Het-1A cells transfected with either SLURP-1 or -2 vector produced the highest amounts of respective proteins between 24 and 48 h, at which point they were exposed to 1 microM NNK for 24 h and their tumorigenic activities were subsequently evaluated by plating in soft agar and injecting subcutaneously to Nu/Nu mice. Transfection with either SLURP-1 or -2 cDNA in both cases significantly (p<0.05) diminished the number of colonies produced by NNK exposed cells. SLURP-1 was more efficient than SLURP-2 in abolishing the tumorigenic effect in nude mice. Thus, the anti-tumorigenic activities of SLURP-1 and -2 were demonstrated both in vitro and in vivo. The obtained results suggest that SLURP-like proteins may become useful for developing novel anti-cancer therapies.
Arredondo
Juan
J
Department of Dermatology, University of California at Irvine, Irvine, CA 92697, USA.
Chernyavsky
Alex I
AI
Grando
Sergei A
SA
D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly / Q000502:physiology*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D058851:GPI-Linked Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D009062:Mouth Neoplasms / Q000517:prevention & control*; D009602:Nitrosamines / Q000633:toxicity*; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D002273:Carcinogens; D058851:GPI-Linked Proteins; C485626:LYNX1 protein, human; D008562:Membrane Glycoproteins; D009602:Nitrosamines; C048963:SLURP1 protein, human; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D014568:Urokinase-Type Plasminogen Activator