Reger de Moura Coralie, Landras Alexandra, Khayati Farah, Maskos Uwe, Maouche Kamel, Battistella Maxime, Menashi Suzanne, Lebbé Céleste, Mourah Samia
Inserm, UMR_S976, Université de Paris, 75010 Paris, France.
Pharmacogenomics Department, Saint Louis Hospital, AP-HP, 75010 Paris, France.
Cancers (Basel). 2021 Sep 28;13(19):4859. doi: 10.3390/cancers13194859.
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.
恶性黑色素瘤是最具侵袭性的皮肤癌之一，其特征为早期淋巴结转移以及产生对治疗的耐药性。因此，通过促进淋巴管形成的机制来理解淋巴管生成的调控，代表了一种转移性癌症的治疗策略。我们之前已经表明，CD147是一种在黑色素瘤中过表达的跨膜糖蛋白，它调节内皮细胞中的血管生成过程。在本研究中，我们显示了人类黑色素瘤淋巴结中CD147高表达水平与表达LYVE-1、Podoplanin和VEGFR-3的淋巴管数量之间的相关性。CD147通过PROX-1转录因子上调体外淋巴管生成及其相关介质。在黑色素瘤模型中的体内研究证实，CD147通过与体外类似的机制参与转移。这项研究证明了CD147在淋巴管生成过程中的旁分泌作用，表明CD147可能是抑制黑色素瘤相关淋巴管生成的一个有前景的靶点。
