A distinct role for interleukin-6 as a major mediator of cellular adjustment to an altered culture condition.
Tissue microenvironment adjusts biological properties of different cells by modulating signaling pathways and cell to cell interactions. This study showed that epithelial-mesenchymal transition (EMT)/ mesenchymal-epithelial transition (MET) can be modulated by altering culture conditions. HPV E6/E7-transfected immortalized oral keratinocytes (IHOK) cultured in different media displayed reversible EMT/MET accompanied by changes in cell phenotype, proliferation, gene expression at transcriptional, and translational level, and migratory and invasive activities. Cholera toxin, a major supplement to culture medium, was responsible for inducing the morphological and biological changes of IHOK. Cholera toxin per se induced EMT by triggering the secretion of interleukin 6 (IL-6) from IHOK. We found IL-6 to be a central molecule that modulates the reversibility of EMT based not only on the mRNA level but also on the level of secretion. Taken together, our results demonstrate that IL-6, a cytokine whose transcription is activated by alterations in culture conditions, is a key molecule for regulating reversible EMT/MET. This study will contribute to understand one way of cellular adjustment for surviving in unfamiliar conditions.
Department of Dental Hygiene, Division of Health science, Yeungnam University College, Daegu, Korea.|Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Hwa-Kyung
HK
Son
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Iha
I
Park
Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Jue Young
JY
Kim
Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Do Kyeong
DK
Kim
Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya, Sri Lanka.
Rasika P
RP
Illeperuma
Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Jung Yoon
JY
Bae
Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Doo Young
DY
Lee
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
Eun-Sang
ES
Oh
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
Da-Woon
DW
Jung
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
Darren R
DR
Williams
Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus Project, Yonsei University, College of Dentistry, Seoul, Korea.
Jin
J
Kim
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D060833:Cellular Microenvironment; D002772:Cholera Toxin / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000637:transplantation; D061986:MCF-7 Cells; D009368:Neoplasm Transplantation; D010641:Phenotype; D015854:Up-Regulation; D015027:Zebrafish / Q000196:embryology
D003470:Culture Media; C508600:IL6 protein, human; D015850:Interleukin-6; D002772:Cholera Toxin
CHOLERA TOXIN; CULTURE CONDITION; EPITHELIAL MESENCHYMAL TRANSITION (EMT); IL-6; MESENCHYMAL EPITHELIAL TRANSITION (MET)