Treatment of Cultured Sebocytes with an EGFR Inhibitor Does Not Lead to Significant Upregulation of Inflammatory Biomarkers
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Epidermal growth factor receptor (EGFR)inhibitors are being used to treat malignancies originating from epithelia. Unfortunately, blocking the EGFR pathway leads to various side effects, most frequently acneiform eruptions. Objective: To probe the mechanism underlying this side effect, we investigated the effect of EGFR inhibitors on cultured sebocytes. Methods: To examine the effects of an EGFR inhibitor (cetuximab, ErbituxⓇ 10 ng/ml) and the effects of EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming growth factor-α (TGF-α,5 ng/ml), on the production of inflammatory cytokines in cultured sebocytes, we used reverse transcriptase-polymerase chain reaction, immunocytofluorescence and Western blots. Outcomes included the expression of interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPAR-γ) and EGFR. Results: There were no significant differences in the expression of IL-1, IL-6, TNF-α, PPAR-γ and EGFR between (a) groups treated with an EGFR inhibitor or an EGFR ligand and (b) the control group, except for a significant increase in the expression of IL-1 in the EGF-treated group. Conclusion:EGFR inhibitors and EGFR ligands do not provoke the expression of inflammatory biomarkers in cultured sebocytes. The role of the sebaceous glands in EGFR inhibitor-induced acneiform eruption should be investigated more thoroughly. (Ann Dermatol 23(1) 12∼18, 2011)
Abstract
Background: Epidermal growth factor receptor (EGFR)inhibitors are being used to treat malignancies originating from epithelia. Unfortunately, blocking the EGFR pathway leads to various side effects, most frequently acneiform eruptions. Objective: To probe the mechanism underlying this side effect, we investigated the effect of EGFR inhibitors on cultured sebocytes. Methods: To examine the effects of an EGFR inhibitor (cetuximab, ErbituxⓇ 10 ng/ml) and the effects of EGFR ligands, such as epidermal growth factor (EGF, 10 ng/ml) and transforming growth factor-α (TGF-α,5 ng/ml), on the production of inflammatory cytokines in cultured sebocytes, we used reverse transcriptase-polymerase chain reaction, immunocytofluorescence and Western blots. Outcomes included the expression of interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPAR-γ) and EGFR. Results: There were no significant differences in the expression of IL-1, IL-6, TNF-α, PPAR-γ and EGFR between (a) groups treated with an EGFR inhibitor or an EGFR ligand and (b) the control group, except for a significant increase in the expression of IL-1 in the EGF-treated group. Conclusion:EGFR inhibitors and EGFR ligands do not provoke the expression of inflammatory biomarkers in cultured sebocytes. The role of the sebaceous glands in EGFR inhibitor-induced acneiform eruption should be investigated more thoroughly. (Ann Dermatol 23(1) 12∼18, 2011)
참고문헌 (27)
- Duvic M, "EGFR inhibitor-associated acneiform folliculitis: assessment and management", Am J Clin Dermatol, 9, pp.285~294 (2008)
- Gutzmer R, "Cutaneous side effects of EGF-receptor inhibition and their management", Hautarzt, 57, pp.509~513 (2006)
- Li T, "Skin toxicities associated with epidermal growth factor receptor inhibitors", Target Oncol, 4, pp.107~119 (2009)
- Molinari E, "Cetuximab-induced acne", Dermatology, 211, pp.330~333 (2005)
- Segaert S, "Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors", Ann Oncol, 16, pp.1425~1433 (2005)
- Pastore S, "The epidermal growth factor receptor system in skin repair and inflammation", J Invest Dermatol, 128, pp.1365~1374 (2008)
- Galimont-Collen AF, "Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors", Eur J Cancer, 43, pp.845~851 (2007)
- Moore GP, "Hair growth induction: roles of growth factors", Ann N Y Acad Sci, 642, pp.308~325 (1991)
- Di Gennaro E, "Critical role of both p27KIP1 and p21CIP1", WAF1 in the antiproliferative effect of ZD1839 (‘Iressa’), an epidermal growth factor receptor tyrosine kinase inhibitor, in head and neck squamous carcinoma cells, 2003, pp.195, 139~150
- Higashiyama S, "Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands", Cancer Sci, 99, pp.214~220 (2008)
- Hu JC, "Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management", J Am Acad Dermatol, 56, pp.317~326 (2007)
- Mascia F, "Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation", Am J Pathol, 163, pp.303~312 (2003)
- Fujie T, "Culture of cells derived from the human sebaceous gland under serum-free conditions without a biological feeder layer or specific matrices", Arch Dermatol Res, 288, pp.703~708 (1996)
- Siebert PD, "Modified acid guanidinium thiocyanate-phenol-chloroform RNA extraction method which greatly reduces DNA contamination", Nucleic Acids Res, 21, pp.2019~2020 (1993)
- Pastore S, "ERK1", 2 regulates epidermal chemokine expression and skin inflammation, 2005, pp.174, 5047~5056
- Cabodi S, "Integrin regulation of epidermal growth factor (EGF) receptor and of EGF-dependent responses", Biochem Soc Trans, 32, pp.438~442 (2004)
- Pullar CE, "The beta2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms", J Cell Sci, 119, pp.592~602 (2006)
- Yahata Y, "A novel function of angiotensin II in skin wound healing. Induction of fibroblast and keratinocyte migration by angiotensin II via heparin-binding epidermal growth factor (EGF)-like growth factor-mediated EGF receptor transactivation", J Biol Chem, 281, pp.13209~13216 (2006)
- Baselga J, "Why the epidermal growth factor receptor? The rationale for cancer therapy", Oncologist, 7(4), pp.2~8 (2002)
- Castillo L, "Pharmacological background of EGFR targeting", Ann Oncol, 15, pp.1007~1012 (2004)
- Ling YH, "Erlotinib, an effective epidermal growth factor receptor tyrosine kinase inhibitor, induces p27KIP1 up-regulation and nuclear translocation in association with cell growth inhibition and G1", S phase arrest in human non-small-cell lung cancer cell lines, 2007, pp.72, 248~258
- Ocvirk J, "Management of cutaneous side-effects of cetuximab therapy in patients with metastatic colorectal cancer", J Eur Acad Dermatol Venereol, 24, pp.453~459 (2010)
- Harding J, "Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody", Drugs Today (Barc), 41, pp.107~127 (2005)
- Vallbohmer D, "Epidermal growth factor receptor as a target for chemotherapy", Clin Colorectal Cancer, 5(1), pp.19~27 (2005)
- Lacouture ME, "Mechanisms of cutaneous toxicities to EGFR inhibitors", Nat Rev Cancer, 6, pp.803~812 (2006)
- Surguladze D, "Tumor necrosis factor-alpha and interleukin-1 antagonists alleviate inflammatory skin changes associated with epidermal growth factor receptor antibody therapy in mice", Cancer Res, 69, pp.5643~5647 (2009)
- Lee WJ, "Influence of substance-P on cultured sebocytes", Arch Dermatol Res, 300, pp.311~316 (2008)