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  • Raccosta, L, et al. (författare)
  • The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
  • 2013
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 210:9, s. 1711-1728
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs. We report that tumor-derived oxysterols recruit protumor neutrophils in a liver X receptor (LXR)–independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression. We demonstrate that interfering with the oxysterol–CXCR2 axis delays tumor growth and prolongs the overall survival of tumor-bearing mice. These results identify an unanticipated protumor function of the oxysterol–CXCR2 axis and a possible target for cancer therapy.
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  • Juhlin, C, et al. (författare)
  • Loss of parafibromin expression in a subset of parathyroid adenomas
  • 2006
  • Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:2, s. 509-523
  • Tidskriftsartikel (refereegranskat)abstract
    • Inactivation of the hyperparathyroidism–jaw tumour syndrome (HPT– JT) gene, HRPT2, was recently established as a genetic mechanism in the development of parathyroid tumours. Its encoded protein parafibromin has tumour-suppressor properties that play an important role in tumour development in the parathyroids, jaws and kidneys. Inactivating HRPT2 mutations are common in HPT– JT and parathyroid carcinomas, and have been described in a few cases of parathyroid adenomas with cystic features. In this study, 46 cases of cystic parathyroid adenomas previously investigated for HRPT2 mutations were characterized with regard to MEN1 gene mutations, cyclin D1 expression and parafibromin expression. In normal tissues and cell lines, parafibromin was ubiquitously expressed. Furthermore, parafibromin was detected as a dominating nuclear and a weaker cytoplasmic signal in transfected cell lines. In the three parathyroid tumours with inactivating HRPT2 mutations parafibromin expression was not detectable, and in one of two cases with aberrantly sized parafibromin the protein was delocalized. Both high and low cyclin D1 levels were found among HRPT2-mutated and -unmutated tumours, suggesting that these events are not mutually exclusive in parathyroid tumour development. The presented data suggest that in the majority of benign parathyroid tumours the expression of parafibromin remains unaltered, while the loss of parafibromin expression is strongly indicative of gene inactivation through mutation of the HRPT2 gene.
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  • Resultat 1-10 av 44

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