Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: Role of osteopontin

Melissa Lazar, Jennifer Sullivan, Galina Chipitsyna, Tamer Aziz, Ahmed F. Salem, Qiaoke Gong, Agnes Witkiewicz, David T. Denhardt, Charles J. Yeo, Hwyda A. Arafat

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein (MCP)-1 and evaluated the role of OPN in mediating these effects. Methods: MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3-300 nmol/L) or OPN (0.15-15 nmol/L) were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase-labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry. Results: Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P < .05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60% of invasive PDA lesions, of whom 66% were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA. Conclusion: Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation by inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects.

Original languageEnglish (US)
Pages (from-to)298-309
Number of pages12
JournalSurgery
Volume148
Issue number2
DOIs
StatePublished - 2010

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Osteopontin
Chemokine CCL2
Nicotine
Adenocarcinoma
Inflammation
Messenger RNA
Proteins
Luciferases
Recombinant Proteins
Smoke
Tobacco Products
Small Interfering RNA
Fluorescent Antibody Technique
Transfection
Real-Time Polymerase Chain Reaction
Protein Isoforms
Smoking
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

ASJC Scopus subject areas

  • Surgery

Cite this

Lazar, M., Sullivan, J., Chipitsyna, G., Aziz, T., Salem, A. F., Gong, Q., ... Arafat, H. A. (2010). Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: Role of osteopontin. Surgery, 148(2), 298-309. https://doi.org/10.1016/j.surg.2010.05.002

Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells : Role of osteopontin. / Lazar, Melissa; Sullivan, Jennifer; Chipitsyna, Galina; Aziz, Tamer; Salem, Ahmed F.; Gong, Qiaoke; Witkiewicz, Agnes; Denhardt, David T.; Yeo, Charles J.; Arafat, Hwyda A.

In: Surgery, Vol. 148, No. 2, 2010, p. 298-309.

Research output: Contribution to journalArticle

Lazar, M, Sullivan, J, Chipitsyna, G, Aziz, T, Salem, AF, Gong, Q, Witkiewicz, A, Denhardt, DT, Yeo, CJ & Arafat, HA 2010, 'Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: Role of osteopontin', Surgery, vol. 148, no. 2, pp. 298-309. https://doi.org/10.1016/j.surg.2010.05.002
Lazar, Melissa ; Sullivan, Jennifer ; Chipitsyna, Galina ; Aziz, Tamer ; Salem, Ahmed F. ; Gong, Qiaoke ; Witkiewicz, Agnes ; Denhardt, David T. ; Yeo, Charles J. ; Arafat, Hwyda A. / Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells : Role of osteopontin. In: Surgery. 2010 ; Vol. 148, No. 2. pp. 298-309.
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title = "Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: Role of osteopontin",
abstract = "Background: Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein (MCP)-1 and evaluated the role of OPN in mediating these effects. Methods: MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3-300 nmol/L) or OPN (0.15-15 nmol/L) were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase-labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry. Results: Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P < .05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60{\%} of invasive PDA lesions, of whom 66{\%} were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA. Conclusion: Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation by inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects.",
author = "Melissa Lazar and Jennifer Sullivan and Galina Chipitsyna and Tamer Aziz and Salem, {Ahmed F.} and Qiaoke Gong and Agnes Witkiewicz and Denhardt, {David T.} and Yeo, {Charles J.} and Arafat, {Hwyda A.}",
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AU - Lazar, Melissa

AU - Sullivan, Jennifer

AU - Chipitsyna, Galina

AU - Aziz, Tamer

AU - Salem, Ahmed F.

AU - Gong, Qiaoke

AU - Witkiewicz, Agnes

AU - Denhardt, David T.

AU - Yeo, Charles J.

AU - Arafat, Hwyda A.

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N2 - Background: Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein (MCP)-1 and evaluated the role of OPN in mediating these effects. Methods: MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3-300 nmol/L) or OPN (0.15-15 nmol/L) were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase-labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry. Results: Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P < .05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60% of invasive PDA lesions, of whom 66% were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA. Conclusion: Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation by inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects.

AB - Background: Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein (MCP)-1 and evaluated the role of OPN in mediating these effects. Methods: MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3-300 nmol/L) or OPN (0.15-15 nmol/L) were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase-labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry. Results: Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P < .05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60% of invasive PDA lesions, of whom 66% were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA. Conclusion: Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation by inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects.

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