TY - JOUR
T1 - Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma
AU - Karoubi, Golnaz
AU - Cortes-Dericks, Lourdes
AU - Gugger, Mathias
AU - Galetta, Domenico
AU - Spaggiari, Lorenzo
AU - Schmid, Ralph A.
PY - 2010/11/1
Y1 - 2010/11/1
N2 - Background and Objectives 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.
AB - Background and Objectives 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.
KW - adenocarcinoma
KW - cancer stem cells
KW - lung cancer
KW - OCT4A
KW - OCT4B
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U2 - 10.1002/jso.21665
DO - 10.1002/jso.21665
M3 - Article
C2 - 20721963
AN - SCOPUS:78349291802
VL - 102
SP - 689
EP - 698
JO - Journal of Surgical Oncology
JF - Journal of Surgical Oncology
SN - 0022-4790
IS - 6
ER -