SLURP-1 and -2 in normal, immortalized and malignant oral keratinocytes
Open accessAbstract
The secreted mammalian Ly-6/urokinase plasminogen activator receptor-related proteins (SLURP)-1 and -2 are produced by keratinocytes comprising the mucocutaneous epithelium. They regulate in autocrine and paracrine ways cell growth and differentiation through the nicotinic acetylcholine receptors (nAChRs) expressed on the plasma membrane. Keratinocyte nAChRs are targeted by tobacco-derived carcinogenic nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce tumorigenic transformation of Het-1A keratinocytes. In this study we asked if SLURPs could abolish tumorigenic effects of nitrosamines. Preincubation with either recombinant SLURP-1 or -2 in both cases considerably reduced the number of colonies in soft agar, and the number of tumor nodules >0.5 cm in diameter in Nu/Nu mice produced by Het-1A cells treated with nitrosamines. The levels of SLURP-1 and -2 mRNA transcripts in nitrosamine-transformed Het-1A cells as well as in the tumor cell lines SCC-25 and FaDu were significantly (p<0.05) less compared to normal gingival keratinocytes, which are probably the major source of the secreted SLURPs found in a sample of human saliva. The expression of SLURPs was decreased due to gene silencing of different nAChR alpha subunits with small hairpin RNA, suggesting that a positive feedback regulation is altered in malignant cells. Thus, SLURP-1 and -2 are efficient autocrine and paracrine ligands of keratinocyte nAChRs capable of preventing tobacco nitrosamine-induced malignant transformation of oral cells. These "proof-of-concept" preliminary results have salient clinical implications.
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SLURPs enhance nicotine-stimulated proliferation of lymphocytes and keratinocytes as well as oral and lung cancer cell proliferation.
“SLURPs enhance this process (123) as well as oral and lung cancer cell proliferation (124).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [124]
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- Authors
- Arredondo, J., Chernyavsky, A. I., & Grando, S. A.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Grando, Sergei A.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 80
- Issue
- 24-25
- Pages
- 2243-2247
- ISSN
- 0024-3205 (ISSN-L)
- PMC
- PMC1929016
- OpenAlex
- W2067182083
- Cited by
- 66
- References
- 11
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 6
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Flight Attendant Medical Research Institute
- National Institutes of Health
- National Cancer Institute (CA117327, R03CA117327)
- National Institute of Environmental Health Sciences (R21ES014384, ES014384)
- National Institute of Dental and Craniofacial Research (R01DE014173, DE14173)
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- SLURP-1, oral keratinocytes, nicotinic acetylcholine receptors, nitrosamines, NNK, NNN, tumorigenic transformation, oral cancer prevention, autocrine and paracrine signaling, gene silencing, shRNA, gingival keratinocytes, saliva, Het-1A cells, FaDu cells
- MeSH terms
- Antigens, Ly, Cells, Cultured, Humans, Membrane Glycoproteins, Mouth Mucosa, Nitrosamines, Receptors, Nicotinic, Recombinant Proteins, Transfection, Urokinase-Type Plasminogen Activator, Immunoblotting, Keratinocytes, Gene Expression, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, GPI-Linked Proteins
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