Research
Print page Print page
Switch language
Bispebjerg Hospital - a part of Copenhagen University Hospital
Published

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Effectiveness and safety of switching from originator to biosimilar adalimumab in patients with psoriasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Overall Survival in Mycosis Fungoides: A Systematic Review and Meta-Analysis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety of neoplasms but their role in BCC is poorly understood.

METHODS: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical and immunofluorescent staining were performed to validate the NGS results and to investigate CAF-related cyto-and chemokines.

RESULTS: NGS revealed upregulation of 65 genes in BCC coding for extracellular matrix components pointing at CAF-related matrix remodeling. qRT-PCR showed increased mRNA expression of CAF markers FAP-α, PDGFR-β and prolyl-4-hydroxylase in BCC. Peritumoural skin (but not buttock skin) also exhibited high expression of PDGFR-β and prolyl-4-hydroxylase but not FAP-α. We found a similar pattern for the CAF-associated chemokines CCL17, CCL18, CCL22, CCL25, CXCL12 and IL6 with high expression in BCC and peritumoural skin but absence in buttock skin. Immunofluorescence revealed correlation between FAP-α and PDGFR-β and CXCL12 and CCL17.

CONCLUSION: Matrix remodeling is the most prominent molecular feature of BCC. CAFs are present within BCC stroma and associated with increased expression of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.

Original languageEnglish
Article number675
JournalB M C Cancer
Volume17
Issue number1
ISSN1471-2407
DOIs
Publication statusPublished - 7 Oct 2017

    Research areas

  • Journal Article

ID: 52415454