Xeroderma Pigmentosum Type C Primary Skin Fibroblasts Overexpress HGF and Promote Squamous Cell Carcinoma Invasion in the Absence of Genotoxic Stress

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Oct 16

PMID 39409898

Authors

Sahar Al-Qaraghuli

Yannick Gache

Maria Goncalves-Maia

Damien Alcor

Elodie Muzotte

Walid Mahfouf

Hamid-Reza Rezvani

Thierry Magnaldo

Affiliations

Soon will be listed here.

Abstract

Xeroderma pigmentosum (XP) is a very rare recessive disease caused by the incapacity to resolve ultraviolet-induced DNA lesions through Nucleotide Excision Repair (NER). Most XP patients suffer from aggressive skin carcinoma and melanoma at a very early age (<8). Our previous results showed that primary XP fibroblasts isolated from healthy (non-photo-exposed) skin negatively impact the extracellular matrix and fail to activate the innate immune system. Here, we show for the first time that XP-C fibroblasts also play a major role in cancer cell invasion ex vivo and in vivo through the overexpression of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in the absence of genotoxic attacks. The use of inhibitors of the activation of the HGF/SF pathway counteracted the effects of XP fibroblasts on the growth of cancer cells, suggesting new perspectives in the care of XP patients.

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