Normal and cancer fibroblasts differentially regulate TWIST1, TOX and cytokine gene expression in cutaneous T-cell lymphoma

• Published in: BMC cancer 2021-05, Vol.21 (1), p.492-492, Article 492
• Main Authors: Mehdi, Syed Jafar, Moerman-Herzog, Andrea, Wong, Henry K
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Aged; Bias; Biomarkers; Cancer; Cancer-Associated Fibroblasts - metabolism; Cancer-Associated Fibroblasts - pathology; Cell culture; Cell Line, Tumor; Cellular Senescence; Chemokines; Coculture Techniques; Cutaneous T cell lymphoma; Cytokines; Development and progression; Endopeptidases - genetics; Endopeptidases - metabolism; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; GATA-3 protein; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene Expression; Genetic aspects; Health aspects; High Mobility Group Proteins - genetics; High Mobility Group Proteins - metabolism; Humans; Immunohistochemistry; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin 1; Interleukin 16; Interleukin 4; Interleukin-16 - genetics; Interleukin-16 - metabolism; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Ligands; Lymphocytes; Lymphocytes T; Lymphoma; Lymphoma, T-Cell, Cutaneous - genetics; Lymphoma, T-Cell, Cutaneous - metabolism; Lymphoma, T-Cell, Cutaneous - pathology; Male; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Mycosis; Mycosis fungoides; Mycosis Fungoides - genetics; Mycosis Fungoides - metabolism; Mycosis Fungoides - pathology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology, Experimental; Patients; Phenotypes; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Senescence; Skin; Skin - cytology; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; T-cell lymphoma; T-Lymphocytes - metabolism; Transcription factors; Tumor Microenvironment; Tumorigenesis; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Vimentin - genetics; Vimentin - metabolism
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-08142-7

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