Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells
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Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells. / Kobold, Sebastian; Völk, Stefanie; Clauditz, Till; Küpper, Natascha Jennifer; Minner, Sarah; Tufman, Amanda; Düwell, Peter; Lindner, Michael; Koch, Ina; Heidegger, Simon; Rothenfuer, Simon; Schnurr, Max; Huber, Rudolf Maria; Wilczak, Waldemar; Endres, Stefan.
In: J THORAC ONCOL, Vol. 8, No. 8, 01.08.2013, p. 1032-42.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells
AU - Kobold, Sebastian
AU - Völk, Stefanie
AU - Clauditz, Till
AU - Küpper, Natascha Jennifer
AU - Minner, Sarah
AU - Tufman, Amanda
AU - Düwell, Peter
AU - Lindner, Michael
AU - Koch, Ina
AU - Heidegger, Simon
AU - Rothenfuer, Simon
AU - Schnurr, Max
AU - Huber, Rudolf Maria
AU - Wilczak, Waldemar
AU - Endres, Stefan
PY - 2013/8/1
Y1 - 2013/8/1
N2 - INTRODUCTION: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients.METHODS: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay.RESULTS: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed.CONCLUSION: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype.
AB - INTRODUCTION: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients.METHODS: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay.RESULTS: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed.CONCLUSION: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Large Cell
KW - Cell Line, Tumor
KW - Child
KW - Drug Resistance, Neoplasm
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Interleukins
KW - Lung Neoplasms
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Receptors, Interleukin
KW - Small Cell Lung Carcinoma
U2 - 10.1097/JTO.0b013e31829923c8
DO - 10.1097/JTO.0b013e31829923c8
M3 - SCORING: Journal article
C2 - 23774470
VL - 8
SP - 1032
EP - 1042
JO - J THORAC ONCOL
JF - J THORAC ONCOL
SN - 1556-0864
IS - 8
ER -