Abstract
BackgroundTumour stroma consists of a heterogeneous population of fibroblasts and related mesenchymal cells, collectively dubbed cancer-associated fibroblasts (CAFs). These CAFs are key players in cancer invasion of cutaneous squamous cell carcinoma (SCC). As we have shown earlier, papillary and reticular fibroblasts (Pfs and Rfs, respectively) have distinct effects on epidermal and dermal homeostasis, but their role in cancer invasion and epithelial-to-mesenchymal transition (EMT) remains to be determined.MethodsWe used 3D cultures of human skin equivalents (HSEs) to analyse the effects of Pfs and Rfs on the invasive behaviour of SCC and EMT.ResultsWe reveal for the first time the importance of Pfs versus Rfs in SCC invasion and EMT. Cell lines from different stages of SCC showed significantly more extensive invasion into a dermis composed of Rfs than of Pfs. In addition, Rfs-based HSEs showed increased cell activation and stained positive for CAF biomarkers α-SMA and vimentin. Further analysis revealed that invasively growing cancer cells in Rf-HSEs express markers of EMT transition, like SNAIL2, N-cadherin and ZEB1.ConclusionsConversely, our results show that Pfs contain cancer cells more within the epidermis. Rfs are clearly predisposed to differentiate into CAFs upon SCC signals, assisting invasion and EMT.
Highlights
The crosstalk between the different components in the tumour microenvironment is recognised as essential in cancer development and is becoming the main focus in cancer research.[1]
Fibroblast heterogeneity in squamous cell carcinoma (SCC) tumour stroma We examined the presence of Pfs and Rfs and epithelial-to-mesenchymal transition (EMT)-related biomarkers in SCC skin biopsies (N = 8)
In vitro effect of fibroblast subpopulations on SCC invasion we examined the effect of Rfs and Pfs on the invasive behaviour of SCC using full-thickness skin models (FTMs) that are generated with a dermal matrix comprising Rfs (Rf-FTMs) or Pfs (Pf-FTMs)
Summary
The crosstalk between the different components in the tumour microenvironment is recognised as essential in cancer development and is becoming the main focus in cancer research.[1]. EMT is crucial for the migration and invasion of cancer cells.[4] a cell loses its epithelial phenotype and tight cell–cell junctions and acquires a mesenchymal phenotype that allows detachment and migration from the primary tumour into the surrounding stroma.[5] Certain fibroblasts, abundant in the tumour stroma, are associated with SCC progression; they have structural and functional contributions to this process. These socalled cancer-associated fibroblasts (CAFs) produce growth factors and chemokines, which facilitate angiogenesis, tissue invasion and metastasis. Rfs are clearly predisposed to differentiate into CAFs upon SCC signals, assisting invasion and EMT
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
