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Overexpression Of Interleukin-6 In Human Basal Cell Carcinoma Cell Lines Increases Anti-apoptotic Activity And Tumorigenic Potency

S. Jee, S. Shen, H. Chiu, W. Tsai, M. Kuo
Published 2001 · Biology, Medicine

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Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using 3H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.
This paper references
10.1177/001452469000101110
"J."
G. G. Stokes (1890)
Cancer Treat
P Schlag (1984)
10.1016/0022-4804(90)90224-P
Interleukin-6 production by endotoxin-stimulated Kupffer cells is regulated by prostaglandin E2.
M. Callery (1990)
10.1016/0923-2494(92)80014-C
IL6 and the T-cell response.
F. Houssiau (1992)
10.1111/j.1600-065X.1992.tb01407.x
IL‐6 and NF‐IL6 in Acute‐Phase Response and Viral Infection
S. Akira (1992)
10.1083/JCB.124.1.1
Bcl-2 and the regulation of programmed cell death
J. C. Reed (1994)
Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells.
J. Reynolds (1994)
10.1016/0168-1656(94)90168-6
High-level expression of a biologically active human interleukin-6 mutein.
S. M. Skelly (1994)
Prevention of myeloma cell apoptosis by ectopic bcl-2 expression or interleukin 6-mediated up-regulation of bcl-xL.
M. M. Schwarze (1995)
10.1126/science.7878464
Apoptosis in the pathogenesis and treatment of disease
C. Thompson (1995)
10.1083/JCB.128.6.1173
The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2
T. Yang (1995)
10.1007/978-1-4613-1261-1_9
Interleukin-6: biologic properties and role in lymphoproliferative disorders.
J. Seymour (1996)
Endogenous interleukin 6 can function as an in vivo growth- stimulatory factor for advanced-stage human melanoma cells.
C. Lu (1996)
10.1074/jbc.271.2.736
Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor (*)
T. Cohen (1996)
10.1111/j.1442-2042.1996.tb00560.x
Gene Expression of TGF‐α, EGF and IL‐6 in Cultured Renal Tubular Cells and Renal Cell Carcinoma
T. Aoyagi (1996)
10.1002/JBMR.5650110113
Interleukin‐6 and soluble interleukin‐6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast‐like cell formation
S. Kotake (1996)
10.1159/000237257
Interleukin-6 and the skin.
P. Paquet (1996)
Clin
C Lu (1996)
Arch
HT Yen (1996)
Cancer Treat
JF Seymour (1996)
10.1076/APAB.105.2.125.12927
Apoptose et Gènes Anti-Apoptotiques de la Famille Bcl-2
J. Dietrich (1997)
10.1016/S0168-9525(97)01246-8
Sunlight and the onset of skin cancer.
D. Brash (1997)
10.1002/(SICI)1097-0215(19970703)72:1<149::AID-IJC21>3.0.CO;2-D
Interleukin‐6 functions as an autocrine growth factor in human bladder carcinoma cell lines in vitro
M. Okamoto (1997)
10.1016/S0167-5699(97)01103-1
IL-6 and APPs: anti-inflammatory and immunosuppressive mediators.
H. Tilg (1997)
10.1006/CLIN.1997.4420
IL-6: insights into novel biological activities.
B. Barton (1997)
Int
M Okamoto (1997)
Immunol
H Tilg (1997)
10.1046/j.1365-2133.1998.02404.x
Ultraviolet B radiation‐induced production of interleukin 1α and interleukin 6 in a human squamous carcinoma cell line is wavelength‐dependent and can be inhibited by pharmacological agents
Eberlein‐KÖnig (1998)
10.3109/07435809809032715
The possible role of apoptosis-suppressing genes, bcl-2 and mcl-1/EAT in human adrenal tumors.
T. Ando (1998)
10.1016/S0002-9440(10)65605-2
Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice.
P. Schirmacher (1998)
10.1002/(SICI)1097-4652(199812)177:3<493::AID-JCP12>3.0.CO;2-B
Dose‐dependent induction of IL‐12 but not IL‐10 from human keratinocytes after exposure to ultraviolet light A
S. Kondo (1998)
10.1016/S0092-8674(00)81433-6
Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells
M. Tsujii (1998)
10.1038/sj.onc.1202133
Bcl-2 prevents topoisomerase II inhibitor GL331-induced apoptosis is mediated by down-regulation of poly(ADP-ribose)polymerase activity
M. Kuo (1998)
10.1073/PNAS.95.2.565
UVB-induced association of tumor necrosis factor (TNF) receptor 1/TNF receptor-associated factor-2 mediates activation of Rel proteins.
D. Tobin (1998)
10.1093/emboj/17.19.5588
Coexpression of IL‐6 and soluble IL‐6R causes nodular regenerative hyperplasia and adenomas of the liver
D. Maione (1998)
10.1007/s004030050347
Relationship between keratinocyte adhesion and death: anoikis in acantholytic diseases
R. Gniadecki (1998)
10.1002/(SICI)1097-4652(199809)176:3<648::AID-JCP22>3.0.CO;2-U
Insulin‐like growth factor‐I‐mediated survival from Anoikis: Role of cell aggregation and focal adhesion kinase
B. Valentinis (1998)
10.3201/EID0403.980339
Infectious causes of chronic inflammatory diseases and cancer.
G. Cassell (1998)
Br
B Eberlein-Konig (1998)
Oncogene, 17, 2225 ± 2234
Huang TS. (1998)
Am
P Schirmacher (1998)
UV-A irradiation induces transcription of IL-6 and TNF alpha genes in human keratinocytes and dermal fibroblasts.
E. Avalos-Díaz (1999)
10.1055/S-2007-978703
Insulin and IGF-I receptors signaling in protection from apoptosis.
M. Prisco (1999)
10.1182/BLOOD.V93.12.4034.412K38_4034_4043
Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.
Y. Aoki (1999)
10.1002/(SICI)1097-0142(19990615)85:12<2526::AID-CNCR6>3.0.CO;2-3
Serum interleukin‐6 level reflects the tumor proliferative activity in patients with colorectal carcinoma
T. Kinoshita (1999)
10.1016/S0022-5347(01)62092-5
Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma.
H. Adler (1999)
10.1359/jbmr.1999.14.7.1096
A Novel T Cell Cytokine Stimulates Interleukin‐6 in Human Osteoblastic Cells
L. Rifas (1999)
10.1006/brbi.1999.0565
The Roles of IL-1, IL-6, and TNFα in the Feeding Responses to Endotoxin and Influenza Virus Infection in Mice
A. Świergiel (1999)
10.1038/10552
Mice deficient in tumor necrosis factor-α are resistant to skin carcinogenesis
Robert J. Moore (1999)
10.1093/CARCIN/20.4.727
Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells.
M. Soriani (1999)
10.1128/MCB.19.9.6195
The Antiapoptotic Gene mcl-1 Is Up-Regulated by the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway through a Transcription Factor Complex Containing CREB
Ju-Ming Wang (1999)
10.1161/01.ATV.19.8.1835
Oncostatin M induces angiogenesis in vitro and in vivo.
M. Vasse (1999)
10.1074/jbc.274.33.23013
Interleukin-6 Inhibits Transforming Growth Factor-β-induced Apoptosis through the Phosphatidylinositol 3-Kinase/Akt and Signal Transducers and Activators of Transcription 3 Pathways*
Ruey-Hwa Chen (1999)
Blood, 93, 4034 ± 4043
PS Moore (1999)
Nat
RJ Moore (1999)
Mol
JM Wang (1999)
Horm
M Prisco (1999)
Brain Behav
AH Swiergiel (1999)
Throm
M Vasse (1999)



This paper is referenced by
10.1007/978-3-030-64009-5_3
Molecular Landscape of Skin Carcinomas
A. Czarnecka (2021)
10.18632/aging.103518
Interleukin-6 -174 G/C polymorphism is associated with the risk of basal cell carcinoma in a Chinese Han population
J. Wang (2020)
10.1007/978-3-030-26887-9_5
Local Immunotherapy for Basal Cell Carcinoma with Interferon
H. Doan (2020)
10.3389/fimmu.2019.01676
E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes
Cristina Artaza-Irigaray (2019)
10.1245/s10434-019-07790-1
Curative-Intent Surgery for Stage IV Advanced Gastric Cancer: Who Can Undergo Surgery and What Are the Prognostic Factors for Long-Term Survival?
S. Sato (2019)
10.2147/OPTH.S221911
Expression of interleukin-6 in ocular surface squamous neoplasia
M. Eghtedari (2019)
OPTH_A_221911 1675..1680
M. Eghtedari (2019)
10.1007/s00403-019-01952-7
STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland
M. Sławińska (2019)
10.1038/s41419-018-0375-6
IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation
Jaesuk Yun (2018)
10.7150/jca.15989
Differentiation by NK cells is a prerequisite for effective targeting of cancer stem cells/poorly differentiated tumors by chemopreventive and chemotherapeutic drugs
A. Kozłowska (2017)
Polymorphismes des gènes associés à l’inflammation et microenvironnement tumoral lymphocytaire CD8+ : valeur pronostique dans les carcinomes urothéliaux de la vessie.
Alexandra Masson Lecomte (2017)
6 Genomics of Basal and Squamous Cell Carcinomas
V. Samarasinghe (2017)
10.18632/oncotarget.13629
Targeting the VEGF-C/VEGFR3 axis suppresses Slug-mediated cancer metastasis and stemness via inhibition of KRAS/YAP1 signaling
Yu-Wen Yeh (2017)
10.1007/978-3-319-29785-9_42
Immune Environment of Cutaneous Malignancies
C. Ovits (2017)
10.1007/s11095-016-2036-8
Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer
K. Rehman (2016)
10.1111/dote.12420
Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.
J. Kimura (2016)
10.5650/jos.ess15256
Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells.
K. Rehman (2016)
10.19264/HJ.V27I4.99
C - Reactive Protein and urological malignancies: A systematic review
A. Pappas (2015)
10.1039/c4pp00455h
T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?
F. Anzengruber (2015)
10.1007/s00277-015-2361-8
The prognostic nutritional index predicts survival for patients with extranodal natural killer/T cell lymphoma, nasal type
Kailin Chen (2015)
10.1007/s10555-015-9588-7
Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies
M. Broekgaarden (2015)
10.7314/APJCP.2015.16.14.5687
Factors Prognostic for Survival in Japanese Patients Treated with Sunitinib as First-line Therapy for Metastatic Clear Cell Renal Cell Cancer.
Y. Kawai (2015)
10.1007/s12079-015-0298-2
How do benign myoepithelial cells from in situ areas of carcinoma ex-pleomorphic adenoma favor tumor progression?
E. Martinez (2015)
Immune Response Regulation has Thera- peutic Potential in the Treatment of Cancer
M. Festa (2015)
10.1016/j.pdpdt.2014.01.002
The interrelation between a pro-inflammatory milieu and fluorescence diagnosis or photodynamic therapy of human skin cell lines.
Patrick Larisch (2014)
10.1201/B17288-6
Mechanistic Principles of Photodynamic Therapy
B. Henderson (2014)
10.1016/j.eururo.2012.11.050
The predictive value of C-reactive protein for prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy: a multi-institutional study.
N. Tanaka (2014)
10.1111/cas.12187
Soluble interleukin‐6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy
Yosuke Makuuchi (2013)
10.1097/PPO.0000000000000010
Inflammation and Skin Cancer: Old Pals Telling New Stories
Sabine Hensler (2013)
10.1038/cddis.2013.166
Antitumor activity of IL-32β through the activation of lymphocytes, and the inactivation of NF-κB and STAT3 signals
Hyung-Mun Yun (2013)
10.1016/j.urolonc.2012.05.008
C-reactive protein: a biomarker of survival in patients with localized upper tract urothelial carcinoma treated with radical nephroureterectomy.
J. Obata (2013)
10.1016/j.archoralbio.2012.06.001
In vitro cytokine expression in in situ-like areas of malignant neoplasia.
E. Martinez (2013)
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