Introduction

Cancer-associated fibroblasts (CAFs), a component of tumor microenvironment, play a key role in oncogenesis and promote growth, invasion, metastasis and chemo-resistance of tumor cells. Our previous RNAseq results brought evidence of the contribution of dermal fibroblasts obtained from cutaneous T-cell lymphoma (CTCL) lesions to support tumor growth. Here, we further go on by analyzing the alteration of protein production by dermal fibroblasts obtained from CTCL lesions versus control fibroblasts.

Materials and methods

Secretome and proteome was performed on fibroblast primary cultures skin biopsies of 6 cutaneous T-cell lymphoma (CTCL[GD1] ) versus fibroblasts from healthy mammary skin controls (age-paired). The fibroblasts of the two groups were studied at the 3rd passage, after stimulation or not with 5 ng / ml TGF-β for 24 h. The supernatants and lysates collected underwent enzymatic digestion with trypsin before peptide analysis by HLPC / Mass spectrometry

Results

The comparison of the secretomes from the CTCL groups (± TGF-ß) and the control donors showed a global significant differential expression (fold> 2, p-value <0.05) of 55 proteins. Concerning the proteome, a differential expression of 92 proteins was quantified in control condition and of 146 proteins in stimulated condition (fold> 2, p-value <0.05). The majority of proteins differing between the CTCL patient and control groups were linked to components of the cytoskeleton of fibroblasts. Some sets of molecules were associated with the regeneration of the extracellular matrix and the maintenance of tissue inflammation. The global analysis highlighted 12 main networks and as in previous RNAseq analysis, several pathway-associated sets including “Inhibition of Matrix Metalloproteases” or “Leukocyte Extravasation Signaling” were detected.

Conclusion

The present data demonstrate the potent proteomic alteration of CTCL-associated dermal fibroblasts, confirming the involvement of mesenchymal cells on the behavior of CTCL.