Cancer-Associated Fibroblasts Exert Proangiogenic Activity in Merkel Cell Carcinoma

  • Silvia Albertini
  • Licia Martuscelli
  • Cinzia Borgogna
  • Sanamjeet Virdi
  • Daniela Indenbirken
  • Irene Lo Cigno
  • Gloria Griffante
  • Federica Calati
  • Renzo Boldorini
  • Nicole Fischer (Geteilte/r Letztautor/in)
  • Marisa Gariglio (Geteilte/r Letztautor/in)


The tumor microenvironment is a complex niche enveloping a tumor formed by extracellular matrix, blood vessels, immune cells, and fibroblasts constantly interacting with cancer cells. Although tumor microenvironment is increasingly recognized as a major player in cancer initiation and progression in many tumor types, its involvement in Merkel cell carcinoma (MCC) pathogenesis is currently unknown. In this study, we provide a molecular and functional characterization of cancer-associated fibroblasts (CAFs), the major tumor microenvironment component, in patient-derived xenografts of patients with MCC. We show that subcutaneous coinjection of patient-derived CAFs and human MCC MKL-1 cells into severe combined immunodeficient mice significantly promotes tumor growth and metastasis. These fast-growing xenografts are characterized by areas densely populated with human CAFs, mainly localized around blood vessels. We provide evidence that the growth-promoting activity of MCC-derived CAFs is mediated by the aminopeptidase A/angiotensin II and III/angiotensin II type 1 receptor axis, with the expression of aminopeptidase A in CAFs being a triggering event. Together, our findings point to aminopeptidase A as a potential marker for MCC prognostic stratification and as a candidate for therapeutic intervention.

Bibliografische Daten

StatusVeröffentlicht - 06.2023

Anmerkungen des Dekanats

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

PubMed 36572089