Neuropilin-2 promotes melanoma growth and progression in vivo

Abstract

Tumor cell interactions with their microenvironment, and neighboring endothelial cells in particular, are critical for tumor cell survival and the metastatic process. Within the spectrum of tumors, melanomas are notorious for their ability to metastasize at a relatively early stage of development; however, little is known about the molecular pathways mediating this process. We recently performed a screen to assess critical mediators of melanoma metastasis by evaluating melanoma-endothelial cell communication. Neuropilin-2 (NRP2), a cell surface receptor involved in angiogenesis and axonal guidance, was found to be an important mediator of melanoma-endothelial cell cross-talk in these studies. Here we seek to further define the role of NRP2 in melanoma growth and progression. We use stable gene silencing of NRP2 in melanomas from varying stages of tumor progression to define the role of NRP2 in melanoma growth, migration, invasion, and metastasis. We found that NRP2 gene silencing in metastatic melanoma cell lines inhibited tumor cell growth in vitro; furthermore, knockdown of NRP2 expression in the metastatic melanoma cell line 1205Lu significantly inhibited in-vivo tumor growth and metastasis. We conclude that NRP2 plays an important role in mediating melanoma growth and metastasis and suggest that targeting this cell surface molecule may represent a significant therapeutic strategy for patients diagnosed with aggressive forms of melanoma.

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression

“…This suggested that NRP2 expression modulated by miR-196a-3p has an effect in influencing specific steps in the metastatic cascade. Based on our finding that miR-196a-3p mimics inhibit the metastasis of breast cancer cells, which was reinforced by knockdown of NRP2 and antagonized by TGF-β1 stimulation, and previous reports that NRP2 acts as an oncogene to promote metastasis in cancers such as breast cancer [ 25 ], esophageal squamous cell carcinoma [ 26 ], and melanoma [ 27 ], we hypothesized that miR-196a-3p and its downstream target NRP2 is involved in TGF-β-induced cell migration and invasion in breast cancer. The present study provides evidence confirming the crosstalk between the TGF-β signaling pathway and miRNAs in breast cancer.…”

Enhanced Anticancer Effect of a Combination of S-adenosylmethionine (SAM) and Immune Checkpoint Inhibitor (ICPi) in a Syngeneic Mouse Model of Advanced Melanoma

“…Neuropilins (NRPs) function as coreceptors of the VEGF family and plexins and are involved in promoting angiogenesis and in axonal guidance, respectively ( 45 , 46 ). NRP2 was recently found to be an oncogene involved in accelerating melanoma tumor growth and progression in vivo ( 45 , 46 ). NRP2 showed significantly high expression in the primary tumors and metastatic tissues of the melanoma patient samples although normal tissues had low expression ( Figures 4A,B ).…”

p53-R273H upregulates neuropilin-2 to promote cell mobility and tumor metastasis

“…Multiple reports have indicated a role of NRP2 in cancer metastasis. 36 For instance, NRP2 is shown to promote metastasis in melanoma 37 and to enhance migration of hepatocellular carcinoma cells. 29 In addition, NRP2 promotes metastasis in oesophageal squamous cell carcinoma through deregulation of ERK-MAPK-ETV4-MMP-E-cadherin.…”