PRDM14 is overexpressed in chronic pancreatitis prior to pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma ( PDAC ) is an aggressive and lethal cancer that is typically diagnosed at a later stage with metastases and is difficult to treat. Therefore, investigating the mechanism of PDAC initiation is important to aid early‐stage cancer detection. PRDM 14 is a transcription factor that maintains pluripotency in embryonic stem cells and is overexpressed in several cancers. We previously reported that PRDM 14 is overexpressed and regulates cancer stem‐like phenotypes in PDAC , and herein, we assess whether PRDM 14 expression increases prior to tumorigenesis. Through immunohistochemistry analyses of clinical tissues, we detected PRDM 14‐positive cells in precursor pancreatic intraepithelial neoplasia and chronic pancreatitis, which is a risk factor for PDAC , lesions. PRDM 14 staining in chronic pancreatitis was as high as that in PDAC and cancer adjacent tissues. We induced pancreatitis in mouse models by cerulein injection, and observed that PRDM 14 expression increased in chronic pancreatitis models but not in control or acute pancreatitis mice. Moreover, cerulein treatment increased PRDM 14 expression in PK ‐1 and As PC ‐1 pancreatic cancer cell lines. Our results suggest that inflammation increases the expression of PRDM 14, which regulates cancer stem‐like phenotypes, and this occurs prior to PDAC initiation and progression.

Off to a Bad Start: Cancer Initiation by Pluripotency Regulator PRDM14

“…Consistently, silencing PRDM14 in breast cancer cells inhibits their stem-cell-like properties, ability to cause tumours and prevents metastasis in an immuno-deficient mouse model [13]. Expression of PRDM14 is also associated with progression to pancreatic cancer [14], and its inhibition suppresses pancreatic cancer cell metastasis in an immuno-deficient mouse model [15]. Prdm14 was also identified as the driver mutation in retrovirally-induced mouse lymphoid leukemias.…”

Multifaceted Role of PRDM Proteins in Human Cancer

“…More recently, overexpression of PRDM14 was observed also in pancreatic cancer, where it could sustain cell pluripotency; indeed, PRDM14 knockdown suppressed cancer stem-like phenotypes, including liver metastasis, via miR-125a-3p regulating Fyn expression ( Figure 1F) [200]. Additionally, PRDM14-positive cells were also detected through immunohistochemistry analyses in precursor pancreatic intraepithelial neoplasia and chronic pancreatitis lesions, a pancreatic cancer risk factor [201]. Alterations of the 8q13.2 region with PRDM14 copy number gain were also found in intracranial germ cell tumors [202] and in head and neck cancer [203].…”

Therapeutic siRNA targeting the cancer cell stemness regulator PRDI-BF1 and RIZ domain zinc finger protein 14

“… 10 ) PRDM14 overexpression was observed in pancreatic cancer tissues from patients with chronic pancreatitis as a pre-cancerous region and pancreatic intraepithelial neoplasia: PanIN as early-stage intraductal cancer, compared with normal pancreatic tissues. 12 , 27 )…”