CD147 Promotes Tumor Lymphangiogenesis in Melanoma via PROX-1

Coralie Reger de Moura (1, 2) , Alexandra Landras (1) , Farah Khayati (1) , Uwe Maskos (3) , Kamel Maouche (4) , Maxime Battistella (1, 2) , Suzanne Menashi (2) , Céleste Lebbé (1, 2) , Samia Mourah (1, 2)

1 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
2 AP-HP - Hopital Saint-Louis [AP-HP]
3 NISC - Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems
4 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative

Malignant melanoma is one of the most aggressive skin cancers and is characterized by early lymph node metastasis and the capacity to develop resistance to therapies. Hence, understanding the regulation of lymphangiogenesis through mechanisms contributing to lymphatic vessel formation represents a treatment strategy for metastatic cancer. We have previously shown that CD147, a transmembrane glycoprotein overexpressed in melanoma, regulates the angiogenic process in endothelial cells. In this study, we show a correlation between high CD147 expression levels and the number of lymphatic vessels expressing LYVE-1, Podoplanin, and VEGFR-3 in human melanoma lymph nodes. CD147 upregulates in vitro lymphangiogenesis and its related mediators through the PROX-1 transcription factor. In vivo studies in a melanoma model confirmed that CD147 is involved in metastasis through a similar mechanism as in vitro. This study, demonstrating the paracrine role of CD147 in the lymphangiogenesis process, suggests that CD147 could be a promising target for the inhibition of melanoma-associated lymphangiogenesis

Mots clés: lymphangiogenesis; CD147; melanoma; lymph node metastasis; therapeutic targets

Domaines: Neurosciences

Coralie Reger de Moura, Alexandra Landras, Farah Khayati, Uwe Maskos, Kamel Maouche, et al.. CD147 Promotes Tumor Lymphangiogenesis in Melanoma via PROX-1. Cancers, 2021, This article belongs to the Special Issue New Emerging Connections in Tumor Angiogenesis, Lymphangiogenesis and Their Therapeutic Relevance, 13 (19), pp.4859. ⟨10.3390/cancers13194859⟩. ⟨pasteur-03366235⟩