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Stem Cells in the Exocrine Pancreas during Homeostasis, Injury, and Cancer

期刊

CANCERS
卷 13, 期 13, 页码 -

出版社

MDPI
DOI: 10.3390/cancers13133295

关键词

pancreas; pancreatitis; pancreatic cancer; pancreatic stem cells; stem cell dynamics; microenvironment

类别

资金

  1. New York Stem Cell Foundation
  2. KWF [UVA2014-7245, 10529]
  3. Maurits en Anna de Kock Stichting [2015-2]
  4. Worldwide Cancer Research [14-1164]
  5. Maag Lever Darm Stichting [MLDS-CDG 14-03]
  6. European Research Council [ERG-StG 638193]
  7. ZonMw [Vidi 016.156.308]

向作者/读者索取更多资源

Cell generation and renewal play essential roles in tissue development, maintenance, and regeneration. The pancreas is a dormant organ with limited regeneration capacity, and understanding the underlying mechanisms of pancreatic stem cells may provide insights into the role of cancer stem cells (CSCs) in pancreatic ductal adenocarcinoma (PDAC). Imbalance between cellular proliferation and differentiation can lead to disease initiation, particularly cancer formation.
Cell generation and renewal are essential processes to develop, maintain, and regenerate tissues. New cells can be generated from immature cell types, such as stem-like cells, or originate from more differentiated pre-existing cells that self-renew or transdifferentiate. The adult pancreas is a dormant organ with limited regeneration capacity, which complicates studying these processes. As a result, there is still discussion about the existence of stem cells in the adult pancreas. Interestingly, in contrast to the classical stem cell concept, stem cell properties seem to be plastic, and, in circumstances of injury, differentiated cells can revert back to a more immature cellular state. Importantly, deregulation of the balance between cellular proliferation and differentiation can lead to disease initiation, in particular to cancer formation. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of only similar to 9%. Unfortunately, metastasis formation often occurs prior to diagnosis, and most tumors are resistant to current treatment strategies. It has been proposed that a specific subpopulation of cells, i.e., cancer stem cells (CSCs), are responsible for tumor expansion, metastasis formation, and therapy resistance. Understanding the underlying mechanisms of pancreatic stem cells during homeostasis and injury might lead to new insights to understand the role of CSCs in PDAC. Therefore, in this review, we present an overview of the current literature regarding the stem cell dynamics in the pancreas during health and disease. Furthermore, we highlight the influence of the tumor microenvironment on the growth behavior of PDAC.

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