CD146 is a potential immunotarget for neuroblastoma

Abstract

Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest‐derived immature cells. The prognosis of patients with high‐risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti‐tumor effects of CD146‐targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA‐mediated knockdown of CD146, or treatment with an anti‐CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor‐kappa B signaling pathway. Furthermore, the anti‐CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma.

Identification of potential molecular targets for the treatment of cluster 1 human pheochromocytoma and paraganglioma via comprehensive proteomic characterization

“…In addition to cell surface CD146, soluble sCD146 is released by ectodomain shedding of membrane CD146, which enhances angiogenesis and metastasis [ 21 – 23 ]. The direct effect of CD146 on tumor growth has been demonstrated in several studies using genetic inactivation or inhibition with anti-CD146 blocking antibodies in breast cancer [ 20 ], neuroblastoma [ 24 ] and melanoma [ 22 , 23 , 25 ].…”

CD146‐targeted nuclear medicine imaging in cancer: State of the art

“…A knockdown of CD146 with short hairpin RNA or treatment with an anti‐CD146 polyclonal antibody can effectively inhibit neuroblastoma cell growth. They are halted by increased apoptosis via FAK and/or NF‐κB signaling 67 . CD146 promotes osteosarcoma progression by mediating pro‐tumoral and angiogenic effects 68 …”

“…They are halted by increased apoptosis via FAK and/or NF-κB signaling. 67 CD146 pro-motes osteosarcoma progression by mediating pro-tumoral and angiogenic effects. 68 The expression of CD146 is related to many transcription factors.…”

Efeito de nanovesículas extracelulares derivadas de linhagens tumorais de linfoma T cutâneo em queratinócitos imortalizados

“…Identificamos também outras moléculas de adesão nos preparados de sEV-LCCT, ALCAM/CD166 e MCAM/CD146, com maior abundância na amostra representativa da forma leucêmica SS, sEV-Hut78, em ambos os casos. As duas moléculas podem estar relacionadas com progressão tumoral no LCCT, visto que ALCAM/CD166, tem participação na internalização de sEV tumorais por células receptoras (Cardeñes et al 2022) e a forma solúvel de MCAM/CD146, é relacionada com angiogênese e metástase, sendo considerada mau prognostico em diversos canceres (Du et al 2022, Nollet et al 2022, Sharma et al 2022, Abu El-Asrar et al 2021, Obu et al 2021.…”