Understanding pancreatic cancer stem cells and their role in carcinogenesis: a narrative review

Abstract

Objective: The purpose of this review article is to describe the pathogenesis of pancreatic cancer and to better understand the role of abnormal stem cells in the development of pancreatic cancer.Background: Pancreatic cancer is a highly fatal disease that is caused by the uncontrolled proliferation of pancreatic exocrine or neuroendocrine glands. It is believed that pancreatic cancers arise from a small population of abnormal cancer stem cells (CSCs) that promote tumorigenesis, tumor metastasis and therapeutic resistance. The molecular markers CD133, CXCR4, DCLK1, c-MET, ABCG2 and Lgr5 are routinely used to detected and observe the behaviours of pancreatic cancer stem cells (PCSCs).Methods: A comprehensive search was performed on PubMed, Google Scholar, Scopus, Clinicaltrials.gov and Web of Science using related keywords. Articles focusing on PCSCs and pancreatic cancer pathogenesis, biochemistry and clinical trials were selected.Conclusions: Although very little is known about the exact cause of pancreatic cancer, PCSCs seem to play an important role in carcinogenesis. Mutated biochemical cascades include Sonic Hedgehog, K-RAS-JNK, DLL4/Notch and Nodal/Activin. Several clinical trials are trying to determine if the transplantation of hematopoietic stem cell or peripheral stem cells could be useful for the treatment of such an aggressive tumor.

Umbelliprenin induces autophagy and apoptosis while inhibits cancer cell stemness in pancreatic cancer cells

“…Pancreatic CSCs have been involved in tumor initiation, metastases, recurrence, and drug resistance. Stemness‐associated biomarkers like SOX2, OCT4, Nanog, and increased ALDH activity are responsible for cancer stem cell self‐renew and differentiation and correlated with poor prognosis in pancreatic cancer patients 38 . In the present study, we observed that umbelliprenin greatly decreased the subpopulation of ALDH+ pancreatic CSCs and reduced the number and size of formed stem cell spheres.…”

“…Stemnessassociated biomarkers like SOX2, OCT4, Nanog, and increased ALDH activity are responsible for cancer stem cell self-renew and differentiation and correlated with poor prognosis in pancreatic cancer patients. 38 In the present study, we observed that umbelliprenin greatly decreased the subpopulation of ALDH+ pancreatic CSCs and reduced the number and size of formed stem cell spheres. Umbelliprenin treatment significantly downregulated the mRNA of Oct4, Nanog, and SOX2, suggesting umbelliprenin as a putative pancreatic cancer stem cell killing drug.…”

Recent advances in cancer-associated fibroblast: Biomarkers, signaling pathways, and therapeutic opportunities

“…Sonic hedgehog is a soluble ligand overexpressed by neoplastic cells that drives the formation of a broblast-rich desmoplastic stroma. [62] In the canonical Hh signaling pathway, Hh secreted from epithelial cells activates Smoothened (SMO)-dependent downstream signaling in stromal cells in a paracrine fashion and promotes desmoplasia. [63] The Hh pathway is a major regulator of CAF activation and subsequent desmoplasia, but the precise function of Hh signaling in the TME remains controversial.…”

Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials

“…These abnormal pluripotent stem cells self-renew and give rise to different progenitor cells which aides tumorigenesis, metastasis, and therapy resistance (46)(47)(48). It is believed that CSCs originate from non-neoplastic progenitor cells which acquire non-repairable somatic mutations and differentiated daughter cells that reacquire stem cell-like properties via the epithelial-to-mesenchymal transition (EMT) (49,50). The inherent ability of CSCs to self-renew is tightly controlled by the Wnt/Beta-catenin, Hedgehog, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphatidylinositide 3-kinase (PI3K) signalling pathways (51).…”

“…The inherent ability of CSCs to self-renew is tightly controlled by the Wnt/Beta-catenin, Hedgehog, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphatidylinositide 3-kinase (PI3K) signalling pathways ( 51 ). In CSCs, the TNF-α, TGF-β and IL-1/6 pro-inflammatory cytokines have been observed to modulate EMT by controlling the expression of Snail, Twist and Zeb and other master transcription factors such as STAT3, Smads and NF-kb ( 50 , 52 ).…”