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NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines. | LitMetric

AI Article Synopsis

  • Tumor cell plasticity complicates cancer treatment as it allows tumor cells to adapt and switch phenotypes, potentially leading to more aggressive forms and metastasis.
  • The study found that natural killer (NK) cells can enhance melanoma malignancy by triggering changes associated with epithelial-mesenchymal transition (EMT), such as increased stemness and invasiveness, and inhibiting tumor cell proliferation.
  • NK cells' effects on melanoma cells were linked to specific receptors and cytokines, which also help the tumor cells evade NK-cell attacks, suggesting ways to improve NK cell-based cancer therapies.

Article Abstract

Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelial-mesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometry-based proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells. NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. .

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Source
http://dx.doi.org/10.1158/0008-5472.CAN-17-1891DOI Listing

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