2016
DOI: 10.1038/nature17392
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Abstract: Cancer is a disease of aging, and aged cancer patients have a poorer prognosis. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumor progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression1–4 we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. We find that aged fibr… Show more

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Cited by 297 publications
(265 citation statements)
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“…In these experiments, expression of FL SNPH or Δ-MLS SNPH did not significantly modulate proliferation of Yumm1.7 cells (Supplemental Figure 6H). When reconstituted subcutaneously in syngeneic C57BL/6 mice, Yumm1.7 cells expressing vector disseminated to the lung, as quantified by immunocytochemistry of mCherry reactivity (Figure 6, F and G), and in agreement with recent observations (32). Under these conditions, expression of FL SNPH abolished metastatic seeding of Yumm1.7 cells to the lungs, whereas transfection of Δ-MLS SNPH was associated with increased tumor cell dissemination in vivo (Figure 6, F and G).…”
Section: Identification Of Alternatively Spliced Snph Isoformssupporting
confidence: 77%
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“…In these experiments, expression of FL SNPH or Δ-MLS SNPH did not significantly modulate proliferation of Yumm1.7 cells (Supplemental Figure 6H). When reconstituted subcutaneously in syngeneic C57BL/6 mice, Yumm1.7 cells expressing vector disseminated to the lung, as quantified by immunocytochemistry of mCherry reactivity (Figure 6, F and G), and in agreement with recent observations (32). Under these conditions, expression of FL SNPH abolished metastatic seeding of Yumm1.7 cells to the lungs, whereas transfection of Δ-MLS SNPH was associated with increased tumor cell dissemination in vivo (Figure 6, F and G).…”
Section: Identification Of Alternatively Spliced Snph Isoformssupporting
confidence: 77%
“…For these experiments, we utilized the mCherry-labeled Yumm1.7 cell line, derived from a genetically engineered mouse model of invasive melanoma carrying the genotype Braf V600E ; Cdkn2a -/-;Pten -/- (31) and utilized in recent studies (32). For these experiments, Yumm1.7 cells expressing negligible levels of endogenous SNPH (Supplemental Figure 6F) were stably transfected with vector or SNPH variants and first analyzed for cell motility/proliferation responses in culture.…”
Section: Identification Of Alternatively Spliced Snph Isoformsmentioning
confidence: 99%
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“…Antioxidants inhibit the metastasis of some cell lines (Ferraro et al 2006;Ishikawa et al 2008;Porporato et al 2014). Mouse melanoma cells in an aged microenvironment show decreased APE1 expression as a result of changes in Wnt signaling, which increases ROS, metastasis, and therapy resistance (Kaur et al 2016). Mouse lung carcinoma cells containing mitochondrial DNA with mutations in NADH dehydrogenase subunit 6 (ND6) displayed higher ROS levels and increased metastasis when compared with wild-type mitochondrial DNA and the increase in metastasis could be inhibited by NAC treatment (Ishikawa et al 2008).…”
Section: Ros and Metastasismentioning
confidence: 99%
“…The accumulation of senescent cells with age results in persistent inflammation that contributes to a tumor-permissive environment. Very recently, it was shown that sFRP2 secreted from aged senescent fibroblasts drives therapy resistance of melanoma cells and promotes metastasis (Kaur et al 2016). Whether this is because aged cells have lost their ability to restrain the SASP merits further investigation.…”
mentioning
confidence: 99%