Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

TY - JOUR

T1 - Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

AU - Andreasen, Simon

AU - Therkildsen, Marianne Hamilton

AU - Grauslund, Morten

AU - Friis-Hansen, Lennart

AU - Wessel, Irene

AU - Homøe, Preben

N1 - © 2015 APMIS. Published by John Wiley & Sons Ltd.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize the expression of the pathway components with immunohistochemistry and selected mRNAs and microRNAs (miRNAs) regulated by this pathway in isolated duct- and myoepithelial cells in PA. 46 PAs were immunostained and 10 of these were used for in situ hybridization (ISH). Six frozen specimens were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Using immunohistochemistry, IL-6, JAK1, JAK2 and STAT3 were detected significantly more frequently in PA cells than in cells from normal salivary gland tissue. Using RT-PCR cyclin D1, fibroblast growth factor 2, and p21 were found to be overexpressed while matrix metallopeptidase 9 was detected at low levels in PA compared to normal salivary gland. ISH showed significant overexpression of miR-181b in PA, while miR-21 was undetectable in PA and normal tissue. Overexpression of the pathway components and its mRNA and miRNA products provide important clues regarding the growth of PAs. Our findings brings us one step closer to targeted treatment of this tumor entity, although in vitro studies are warranted to confirm this.

AB - The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize the expression of the pathway components with immunohistochemistry and selected mRNAs and microRNAs (miRNAs) regulated by this pathway in isolated duct- and myoepithelial cells in PA. 46 PAs were immunostained and 10 of these were used for in situ hybridization (ISH). Six frozen specimens were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Using immunohistochemistry, IL-6, JAK1, JAK2 and STAT3 were detected significantly more frequently in PA cells than in cells from normal salivary gland tissue. Using RT-PCR cyclin D1, fibroblast growth factor 2, and p21 were found to be overexpressed while matrix metallopeptidase 9 was detected at low levels in PA compared to normal salivary gland. ISH showed significant overexpression of miR-181b in PA, while miR-21 was undetectable in PA and normal tissue. Overexpression of the pathway components and its mRNA and miRNA products provide important clues regarding the growth of PAs. Our findings brings us one step closer to targeted treatment of this tumor entity, although in vitro studies are warranted to confirm this.

KW - Adenoma, Pleomorphic

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Interleukin-6

KW - Janus Kinase 1

KW - Janus Kinase 2

KW - Male

KW - MicroRNAs

KW - Middle Aged

KW - Parotid Gland

KW - RNA, Messenger

KW - STAT3 Transcription Factor

KW - Signal Transduction

KW - Young Adult

U2 - 10.1111/apm.12407

DO - 10.1111/apm.12407

M3 - Journal article

C2 - 26061266

SN - 0903-4641

VL - 123

SP - 706

EP - 715

JO - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

JF - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

IS - 8

ER -