Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma (CTCL) that transforms from mature, skin-homing T cells and progresses during the early stages in the skin.,The role of the skin microenvironment in MF development is unclear, but recent findings in a variety of cancers have highlighted the role of stromal fibroblasts in promoting or inhibiting tumorigenesis.,Stromal fibroblasts are an important part of the cutaneous tumor microenvironment (TME) in MF.,Here we describe studies into the interaction of TME-fibroblasts and malignant T cells to gain insight into their role in CTCL.,Skin from normal (n = 3) and MF patients (n = 3) were analyzed for FAPα by immunohistochemistry.,MyLa is a CTCL cell line that retains expression of biomarkers TWIST1 and TOX that are frequently detected in CTCL patients.,MyLa cells were cultured in the presence or absence of normal or MF skin derived fibroblasts for 5 days, trypsinized to detached MyL,a cells, and gene expression analyzed by RT-PCR for MF biomarkers (TWIST1 and TOX), Th1 markers (IFNG, TBX21), Th2 markers (GATA3, IL16), and proliferation marker (MKI67).,Purified fibroblasts were assayed for VIM and ACTA2 gene expression.,Cellular senescence assay was performed to assess senescence.,MF skin fibroblast showed increased expression of FAP-α with increasing stage compared to normal.,Normal fibroblasts co-cultured with MyLa cells suppressed expression of TWIST1 (p < 0.0006), and TOX (p < 0.03), GATA3 (p < 0.02) and IL16 (p < 0.03), and increased expression of IFNG (p < 0.03) and TBX21 (p < 0.03) in MyLa cells.,In contrast, MyLa cells cultured with MF fibroblasts retained high expression of TWIST1, TOX and GATA3.,MF fibroblasts co-culture with MyLa cells increased expression of IL16 (p < 0.01) and IL4 (p < 0.02), and suppressed IFNG and TBX21 in MyLa cells.,Furthermore, expression of MKI67 in MyLa cells was suppressed by normal fibroblasts compared to MF fibroblasts.,Skin fibroblasts represent important components of the TME in MF.,In co-culture model, normal and MF fibroblasts have differential influence on T-cell phenotype in modulating expression of Th1 cytokine and CTCL biomarker genes to reveal distinct roles with implications in MF progression.,The online version contains supplementary material available at 10.1186/s12885-021-08142-7.
β-1,4-N-Acetyl-Galactosaminyltransferase 1 (B4GALNT1) encodes the key enzyme B4GALNT1 to generate gangliosides GM2/GD2.,GM2/GD2 gangliosides are surface glycolipids mainly found on brain neurons as well as peripheral nerves and skin melanocytes and are reported to exacerbate the malignant potential of melanomas.,In order to elucidate the mechanism, we performed functional analyses of B4GALNT1-overexpressing cells.,We analyzed ganglioside pattern on four melanoma and two neuroblastoma cell lines by high performance liquid chromatography (HPLC).,We overexpressed B4GALNT1 in GM2/GD2-negative human melanoma cell line (SH4) and confirmed production of GM2/GD2 by HPLC.,They showed higher anchorage independence growth (AIG) in colony formation assay, and exhibited augmented motility.,In vitro, cell proliferation was not affected by GM2/GD2 expression.,In vivo, GM2/GD2-positive SH4 clones showed significantly higher tumorigenesis in NOD/Scid/IL2Rγ-null mice, and immunostaining of mouse CD31 revealed that GM2/GD2 induced remarkable angiogenesis.,No differences were seen in melanoma stem cell and Epithelial-Mesenchymal Transition markers between GM2/GD2-positive and -negative SH4 cells.,We therefore concluded that B4GALNT1, and consequently GM2/GD2, enhanced tumorigenesis via induction of angiogenesis, AIG, and cell motility.,RNA-Seq suggested periostin as a potential key factor for angiogenesis and AIG.,These findings may lead to development of novel therapy for refractory melanoma.