Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma.
OBJECTIVE
Lung cancer is one of the leading causes of cancer-related deaths in the world. Although the origin still remains to be resolved, a prevailing hypothesis implies the involvement of cancer stem cells (CSCs) responsible for tumor initiation, maintenance, and progression. Embryonic stem cell marker, OCT4, encoding the spliced variants OCT4A and OCT4B, has recently been shown to have a dual role; as a potential adult stem cell marker and as a CSC marker in germline and somatic tumors.


METHODS
We investigated the expression and intracellular distribution of OCT4A and OCT4B using flow cytometry, Western blot and quantitative RT-PCR analyses in normal and lung adenocarcinoma cell lines, primary cultures and tissue biopsies.


RESULTS
We demonstrate for the presence of rare OCT4A(+) and OCT4B(+) cells in normal lung. Notably, we observed higher levels of expression and atypical cytoplasmic distribution of OCT4A and not OCT4B, in the malignant setting, strongly indicating an oncogenic role in lung adenocarcinoma.


CONCLUSIONS
We postulate that OCT4A(+) cells are involved in the oncogenesis of lung adenocarcinoma. Identification of these cells and the biological processes vital for their subsistence, will guide the development of diagnostic and therapeutic clinical approaches with the goal of eliminating lung adenocarcinoma.
Karoubi
Golnaz
G
Division of General Thoracic Surgery, Department of Clinical Research, University Hospital Berne, Berne, Switzerland. golnaz.karoubi@dkf.unibe.ch
Cortes-Dericks
Lourdes
L
Gugger
Mathias
M
Galetta
Domenico
D
Spaggiari
Lorenzo
L
Schmid
Ralph A
RA
D000230:Adenocarcinoma / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020033:Protein Isoforms