The texture of collagen in the microenvironments of Merkel cell carcinoma

Abstract

Solid tumors typically contain high levels of fibrillar collagen. The increased stromal collagen deposition usually promotes cancer progression since biochemical and biophysical cues from tumor-associated collagen fibers stimulate neoplastic cells. Few studies have investigated the relationship between Merkel cell carcinoma (MCC) and the extracellular matrix (ECM), but there are no works evaluating collagen.This is an observational, analytical, retrospective study including 11 patients with MCC. Primary tumor-stained sections were evaluated by second harmonic generation microscopy and texture analysis.Peritumoral texture features (area fraction, mean gray value, entropy, and contrast) showed much lower values than normal skin (P < .0001) revealing extensively altered structure of peritumoral collagen fibers. These differences were not significant between tumors with unfavorable and favorable known prognostic factors.Profound changes in collagen fibers present in the stroma accompanying primary MCC may contribute to the aggressive behavior of this tumor. Our results indicate that whatever MCC histological subtype, size or anatomical location, MCC promotes the same type of ECM for its development. As an outlook, therapies using ECM macromolecules or fibroblasts (the architects of ECM remodeling) as target could be useful in the treatment of MCC.

The Role of Extracellular Matrix Remodeling in Skin Tumor Progression and Therapeutic Resistance

“…In primary MCC, an altered scaffold of collagen fibers is in the peritumoral area and possibly contributes to the invasiveness of this tumor. However, surprisingly, collagen expression was independent of prognosis ( Laurito et al, 2021 ). Besides collagen, TNC expression is enhanced in grown tumors and localized at the MCC’s invasive front ( Koljonen et al, 2005 ).…”

The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis

“…Most tissues and organs have a specific type of ECM produced because of the differential expression of ECM genes as well as post-transcriptional splicing and post-translational modifications [ 8 , 9 , 10 , 11 ]. The ECM is in most cases in a state of flux, changing over time because of tissue development and disease [ 12 , 13 , 14 ]. Recent reports indicate that the ECM plays major role in disease progression and the development of chemoresistance [ 15 , 16 , 17 , 18 ].…”

The Extracellular Matrix: Composition, Function, Remodeling and Its Role in Tumorigenesis<i></i>

“…Most tissues and organs have a specific type of ECM produced because of differential expression of ECM genes as well as post-transcriptional splicing and -translational modifications [8][9][10][11]. The ECM is in most cases in a state of flux, changing over time because of tissue development and disease [12][13][14]. Recent reports indicate the ECM play major roles in disease progression and development of chemoresistance [15][16][17][18].…”