title: TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells.
abstract: Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)-beta and during tumorigenesis the apoptotic and growth-inhibitory effects of TGF-betas are lost. Based on these data we investigated the gene expression changes in TGF-betaI-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). As the major sources of TIM-3 ligand galectin-9 are not tumor cells, but rather mast cells, this raises the possibility of an autocrine mechanism resulting in local immunosuppression through the elevated TIM-3 expression by TGF-betaI. Interestingly, not only melanoma tissue sections contained TIM-3-positive mast cells, but we detected this protein also in melanoma cells. Furthermore, TIM-3 was expressed in both WM35 and HT168-M1 melanoma cell lines at a higher level than in isolated epidermal melanocytes, which can contribute to the lower adhering capacity of tumor cells. In conclusion, the immunoregulatory molecule TIM-3 in TGF-beta-stimulated mast cells and melanoma cells may support the survival of this tumor type.
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Wiener
authors.forename: Barbara
authors.initials: B
authors.lastname: Kohalmi
authors.forename: Peter
authors.initials: P
authors.lastname: Pocza
authors.forename: Judit
authors.initials: J
authors.lastname: Jeager
authors.forename: Gergely
authors.initials: G
authors.lastname: Tolgyesi
authors.forename: Sara
authors.initials: S
authors.lastname: Toth
authors.forename: Eva
authors.initials: E
authors.lastname: Gorbe
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Papp
authors.forename: Andras
authors.initials: A
authors.lastname: Falus
mesh_terms: D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D037161:Galectins / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008024:Ligands; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011991:Receptors, Virus / Q000378:metabolism*; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008024:Ligands; D008565:Membrane Proteins; D011991:Receptors, Virus; D053773:Transforming Growth Factor beta1