Cancer-Associated Fibroblasts Exert Proangiogenic Activity in Merkel Cell Carcinoma
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Cancer-Associated Fibroblasts Exert Proangiogenic Activity in Merkel Cell Carcinoma. / Albertini, Silvia; Martuscelli, Licia; Borgogna, Cinzia; Virdi, Sanamjeet; Indenbirken, Daniela; Lo Cigno, Irene; Griffante, Gloria; Calati, Federica; Boldorini, Renzo; Fischer, Nicole; Gariglio, Marisa.
in: J INVEST DERMATOL, Jahrgang 143, Nr. 6, 06.2023, S. 965-976.e15.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cancer-Associated Fibroblasts Exert Proangiogenic Activity in Merkel Cell Carcinoma
AU - Albertini, Silvia
AU - Martuscelli, Licia
AU - Borgogna, Cinzia
AU - Virdi, Sanamjeet
AU - Indenbirken, Daniela
AU - Lo Cigno, Irene
AU - Griffante, Gloria
AU - Calati, Federica
AU - Boldorini, Renzo
AU - Fischer, Nicole
AU - Gariglio, Marisa
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
U2 - 10.1016/j.jid.2022.12.006
DO - 10.1016/j.jid.2022.12.006
M3 - SCORING: Journal article
C2 - 36572089
VL - 143
SP - 965-976.e15
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 6
ER -
