Nestin and other putative cancer stem cell markers in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high incidence of distant metastasis. Recent studies have shown that cancer stem cells (CSCs), which have the potential to self-renew and are pluripotent, are crucially important in cancer cell growth, invasion, metastasis, and recurrence. Recently, several CSC-specific markers for pancreatic cancer have been reported, including CD133, CD24, CD44, CXCR4, EpCAM, ABCG2, c-Met, ALDH-1, and nestin, but their use is controversial. Nestin is one of the class VI intermediate filament proteins and a marker of exocrine progenitors of normal pancreatic tissue. Activated mutations of K-ras in nestin-positive progenitors of pancreatic tissue have been reported to induce cell growth in vitro and induce the formation of precancerous pancreatic lesions. We have reported that downregulation of nestin in PDAC cells inhibits liver metastasis in vivo. Nestin may modulate the invasion and metastasis of nestin-positive progenitor cells during PDAC development and may serve as a novel target for suppressing invasion and metastasis in PDAC. In this review, we summarize what is known about the correlation between PDAC and CSC markers, including nestin.