2016
DOI: 10.18632/aging.101127
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Abstract: Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts i… Show more

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Cited by 84 publications
(77 citation statements)
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“…Similar results were observed in other human fibroblast strains including GM21, LF1, and WI38 cells (Supporting Information Figure S3a). The great majority of cells with prominent α‐SMA expression also displayed discrete DDR foci (over 95%; Figure 3a), suggesting a causal link between DDR induction and myofibroblast transdifferentiation, as reported previously (Dimitrijevic‐Bussod, Balzaretti‐Maggi, & Gadbois, 1999; Mellone et al, 2016; Sampson et al, 2011). However, since not all cells with DDR foci expressed high levels of α‐SMA in stress fibers (Supporting Information Figure S3d), our data also suggested that activation of the DDR alone is not sufficient for myofibroblast transdifferentiation and that other factors, such as timing of DDR induction or long‐term persistence of the DDR, are critical for activating the transdifferentiation program.…”
Section: Resultssupporting
confidence: 84%
See 1 more Smart Citation
“…Similar results were observed in other human fibroblast strains including GM21, LF1, and WI38 cells (Supporting Information Figure S3a). The great majority of cells with prominent α‐SMA expression also displayed discrete DDR foci (over 95%; Figure 3a), suggesting a causal link between DDR induction and myofibroblast transdifferentiation, as reported previously (Dimitrijevic‐Bussod, Balzaretti‐Maggi, & Gadbois, 1999; Mellone et al, 2016; Sampson et al, 2011). However, since not all cells with DDR foci expressed high levels of α‐SMA in stress fibers (Supporting Information Figure S3d), our data also suggested that activation of the DDR alone is not sufficient for myofibroblast transdifferentiation and that other factors, such as timing of DDR induction or long‐term persistence of the DDR, are critical for activating the transdifferentiation program.…”
Section: Resultssupporting
confidence: 84%
“…The observations that a DDR induced by radiation, drugs, or H2O2 similarly promotes myofibroblast transdifferentiation support this conclusion. (Dimitrijevic‐Bussod et al, 1999; Mellone et al, 2016; Sampson et al, 2011). In fact, myofibroblasts have been reported to be nonproliferating cells that show signs of DNA damage (Petrov et al, 2008).…”
Section: Discussionmentioning
confidence: 99%
“…Our results seem to be consistent with a recent study that found that the nonfibrogenic, a-SMAþ myofibroblasts could be directly generated by senescence induction in cancer-associated fibroblasts. 52 Therefore, we propose that the senescence of corneal resident fibroblasts is a programmed wound healing response that functions as a self-limiting mechanism for the prevention of corneal fibrosis. Whether the injured cornea heals with transparency or with scarring depends on the type and level of injury, epithelial basement membrane (EBM) injury, and regeneration.…”
Section: Discussionmentioning
confidence: 99%
“…α-smooth muscle actin (coded for by ACTA2) is a commonly used CAF and myofibroblast marker 16 . However, when identifying myofibroblasts from scRNA-seq data, ACTA2 is not a suitable (single) marker as it is highly expressed by pericytes and smooth muscle cells 17 .…”
Section: Main Textmentioning
confidence: 99%