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  • Hoshino, Ayuko, et al. (författare)
  • Tumour exosome integrins determine organotropic metastasis
  • 2015
  • Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 527:7578, s. 329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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  • Koivula, T, et al. (författare)
  • Acute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients
  • 2023
  • Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 13, s. 1078512-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies have shown that acute exercise can mobilize several leukocyte subpopulations in healthy individuals. Our aim was to investigate whether a 10-min acute exercise has an effect on immune cell proportions in lymphoma patients.Methods: This study included seven lymphoma patients referred to curative oncologic therapy. Three had Hodgkin and four non-Hodgkin lymphoma, one was female, and their mean age was 51. Patients underwent a 10-min acute exercise on a bicycle ergometer at moderate exercise intensity. Whole blood samples were taken at rest, immediately after exercise, and 30 min after exercise. Leukocyte subpopulation levels were determined using flow cytometry.Results: Proportions of total NK cells and CD56+CD16+ NK cells of total leukocytes increased immediately after exercise and decreased back to baseline at 30 min post-exercise. Proportion of CD8+ T cells of total T cells increased and proportion of CD4+ T cells of total T cells decreased immediately after exercise, and both returned to baseline at 30 min post-exercise. There was no change in the proportions of B cells, granulocytes, or monocytes. Exercising diastolic blood pressure correlated positively with changes in total NK cell and CD56+CD16+ NK cell proportions, and exercising mean arterial pressure correlated positively with change in CD56+CD16+ NK cell proportion.Conclusion: Our findings indicate that a single acute exercise bout of only 10 min can cause leukocytosis in lymphoma patients, particularly on cytotoxic T cells and NK cells, which are the most important immune cells fighting against cancer.
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