A1 Refereed original research article in a scientific journal
C5aR1 Promotes Invasion, Metastasis, and Poor Prognosis in Cutaneous Squamous Cell Carcinoma
Authors: Heiskanen, Lauri; Nissinen, Liisa; Siljamäki, Elina; Knuutila, Jaakko S.; Pellinen, Teijo; Kallajoki, Markku; Heino, Jyrki; Riihilä, Pilvi; Kähäri, Veli-Matti
Publisher: Elsevier
Publication year: 2025
Journal: American Journal of Pathology
Journal name in source: The American Journal of Pathology
Volume: 195
Issue: 6
First page : 1158
Last page: 1171
ISSN: 0002-9440
eISSN: 1525-2191
DOI: https://doi.org/10.1016/j.ajpath.2025.02.004
Web address : https://doi.org/10.1016/j.ajpath.2025.02.004
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491615770
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and the metastatic from is associated with a poor prognosis. Here, the role of the complement C5a receptor C5aR1 was examined in the progression and metastasis of cSCC. C5aR1 expression was increased in cSCC cells in a three-dimensional spheroid coculture model in the presence of fibroblasts, and treatment with recombinant C5a enhanced the invasion of cSCC cells. Staining for C5aR1 was detected on the surface of tumor cells at the invasive edge of human cSCC xenografts in vivo. Staining of metastatic and non-metastatic primary human cSCCs, premalignant and benign epidermal lesions, and normal skin for C5aR1 with multiplex immunofluorescence and chromogenic immunohistochemistry revealed increased expression of C5aR1 on the surface of tumor cells and fibroblasts in invasive cSCCs and recessive dystrophic epidermolysis bullosa–associated cSCCs compared with cSCC in situ, actinic keratoses, seborrheic keratoses, and normal skin. Increased expression of C5aR1 on the tumor cell surface and in fibroblasts was associated with metastatic risk and poor disease-specific survival of patients with primary cSCC. These findings suggest a role of C5a in cSCC cell invasion, and they identify C5aR1 as a novel biomarker for metastasis risk and poor prognosis in patients with cSCC. The results also suggest that C5aR1 could be a novel therapeutic target for the treatment of locally advanced and metastatic cSCC.
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