2021
DOI: 10.3389/fcell.2021.743907
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The Cellular Origins of Cancer-Associated Fibroblasts and Their Opposing Contributions to Pancreatic Cancer Growth

Abstract: Pancreatic tumors are known to harbor an abundant and highly desmoplastic stroma. Among the various cell types that reside within tumor stroma, cancer-associated fibroblasts (CAFs) have gained a lot of attention in the cancer field due to their contributions to carcinogenesis and tumor architecture. These cells are not a homogeneous population, but have been shown to have different origins, phenotypes, and contributions. In pancreatic tumors, CAFs generally emerge through the activation and/or recruitment of v… Show more

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Cited by 45 publications
(47 citation statements)
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“…Origin of these cancer-promoting stromal cells has been extensively studied. In addition to the activation of resident fibroblast, PSCs and MSCs, cells from non-fibroblastic lineage such as epithelial cells, endothelial cells, adipocytes, pericytes and smooth muscle cells undergo transdifferentiation to support pancreatic cancer progression ( Manoukian et al, 2021 ). Among these wide variety of cellular origins, PSCs remain numerically minor population of cancer-associated fibroblasts, whereas play nonredundant role such as specific ECM production ( Helms et al, 2022 ).…”
mentioning
confidence: 99%
“…Origin of these cancer-promoting stromal cells has been extensively studied. In addition to the activation of resident fibroblast, PSCs and MSCs, cells from non-fibroblastic lineage such as epithelial cells, endothelial cells, adipocytes, pericytes and smooth muscle cells undergo transdifferentiation to support pancreatic cancer progression ( Manoukian et al, 2021 ). Among these wide variety of cellular origins, PSCs remain numerically minor population of cancer-associated fibroblasts, whereas play nonredundant role such as specific ECM production ( Helms et al, 2022 ).…”
mentioning
confidence: 99%
“…This desmoplastic reaction is regulated via the three major cell types in lesion/tumor areas: lesion cells, macrophages, and fibroblasts ( Storz and Crawford, 2020 ). PDA cancer-associated fibroblasts (CAFs) can have different origins ( Manoukian et al., 2021 ), but one major source is pancreas-resident quiescent stellate cells (qPSCs) ( Apte et al., 2004 ; Bachem et al., 2005 ; Ohlund et al., 2017 ). Recent in vivo lineage tracing using Fabp4-driven Cre indicated that only a portion of CAFs arise from PSCs, but that myCAFs with PSC origins have a tumor-promoting role ( Helms et al., 2021 ).…”
Section: Discussionmentioning
confidence: 99%
“…Other candidate cell types hypothesised as precursors of CAFs and factors stimulating their formation [59][60][61][62][63][64][65] are included in Table 1. Members of the TGF-β family seem to be the most frequently discussed in this context as inducers of the transition of precursor cells to myofibroblasts [66].…”
Section: Origin Of Cafsmentioning
confidence: 99%