2016
DOI: 10.18632/oncotarget.7671
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Abstract: The knowledge on how tumor-associated stroma influences efficacy of anti-cancer therapy just started to emerge. Here we show that lung fibroblasts reduce melanoma sensitivity to the BRAF inhibitor (BRAFi) vemurafenib only if the two cell types are in close proximity. In the presence of fibroblasts, the adjacent melanoma cells acquire de-differentiated mesenchymal-like phenotype. Upon treatment with BRAFi, such melanoma cells maintain high levels of phospho ribosomal protein S6 (pS6), i.e. active mTOR signaling… Show more

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Cited by 28 publications
(32 citation statements)
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“…The potentiated chemoresistance might be associated with the induced EMT. Recently, we have documented such an association in malignant melanoma, which, upon interaction with stromal cells, switched to the mesenchymal phenotype and, simultaneously, became resistant to therapy (Seip et al ., 2016). There could also be other, EMT‐independent mechanisms causing TAM‐like cells to facilitate chemoresistance.…”
Section: Discussionmentioning
confidence: 99%
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“…The potentiated chemoresistance might be associated with the induced EMT. Recently, we have documented such an association in malignant melanoma, which, upon interaction with stromal cells, switched to the mesenchymal phenotype and, simultaneously, became resistant to therapy (Seip et al ., 2016). There could also be other, EMT‐independent mechanisms causing TAM‐like cells to facilitate chemoresistance.…”
Section: Discussionmentioning
confidence: 99%
“…To assess MDA468 cell proliferation, the Luc‐mediated bioluminescence was measured as described previously (Seip et al ., 2016). Briefly, after the addition of 0.1 mg·mL −1 D‐luciferin (Biosynth AG, Staad, Switzerland), bioluminescence was recorded 10 min later by a plate reader, Victor X3 (Perkin Elmer, Waltham, MA, USA).…”
Section: Methodsmentioning
confidence: 99%
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“…In addition to metastasis, Wnt signalling may guide response to multiple forms of therapy in melanoma cells. Wnt inhibitors such as DKK3 are upregulated in dermal fibroblasts co-cultured with melanoma cells treated with BRAF inhibitors, and promote therapy resistance, potentially via β -catenin inactivation (Seip et al , 2016). In support of this, data show that treating dermal fibroblasts with another Wnt inhibitor such as recombinant sFRP2 inhibits their expression of β -catenin, and leads to resistance to BRAF inhibitors in vitro and in vivo .…”
Section: The Wnt Signalling Pathwaysmentioning
confidence: 99%
“…Innate resistance to BRAFi has also been observed particularly in MITF low /AXL high tumors [7,8,16], and the role of CAFs has been reported [17,18]. We have shown in a previous study that the presence of CAFs fosters melanoma cells with reduced sensitivity to BRAFi, and this effect was associated with the phenotypic plasticity [19]. In the current study, we compared molecular features and drug sensitivity in melanoma cells with and without CAFs, with the aim to characterize the CAF-induced phenotype and identify potential nodes for targeting.…”
Section: Introductionmentioning
confidence: 64%