Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells.
Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell-specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4-overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners.
Department of Pharmacy Practice, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
Charn-Jung
CJ
Chang
Yueh
Y
Chien
Kai-Hsi
KH
Lu
Shih-Ching
SC
Chang
Yueh-Ching
YC
Chou
Chi-Shuan
CS
Huang
Chin-Hong
CH
Chang
Kuan-Hsuan
KH
Chen
Yuh-Lih
YL
Chang
Ling-Ming
LM
Tseng
Wen-Shin
WS
Song
Jhi-Joung
JJ
Wang
Jen-Kou
JK
Lin
Pin-I
PI
Huang
Yuan-Tzu
YT
Lan
D019898:Autocrine Communication; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis* / Q000235:genetics
D017077:Culture Media, Conditioned; C496971:IL32 protein, human; D016209:Interleukin-8; D007378:Interleukins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human