WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells

Abstract

Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by a poor prognosis and a low survival rate. Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis and is correlated with cancer metastasis. WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 is an extracellular matrix-related protein that belongs to the CCN family and stimulates many biological functions. Our previous studies showed that WISP-1 plays an important role in OSCC migration and angiogenesis. However, the effect of WISP-1 on VEGF-C regulation and lymphangiogenesis in OSCC is poorly understood. Here, we showed a correlation between WISP-1 and VEGF-C in tissue specimens from patients with OSCC. To examine the lymphangiogenic effect of WISP-1, we used human lymphatic endothelial cells (LECs) to mimic lymphatic vessel formation. The results showed that conditioned media from WISP-1-treated OSCC cells promoted tube formation and cell migration in LECs. We also found that WISP-1-induced VEGF-C is mediated via the integrin αvβ3/integrin-linked kinase (ILK)/Akt signaling pathway. In addition, the expression of microRNA-300 (miR-300) was inhibited by WISP-1 via the integrin αvβ3/ILK/Akt cascade. Collectively, these results reveal the detailed mechanism by which WISP-1 promotes lymphangiogenesis via upregulation of VEGF-C expression in OSCC. Therefore, WISP-1 could serve as therapeutic target to prevent metastasis and lymphangiogenesis in OSCC.

Dysregulation of ß‐catenin, WISP1 and TCF21 predicts disease‐specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck

“…WISP1 promotes angiogenesis via VEGF‐A expression in oral squamous cell carcinoma cells . The protein might be a potential target to prevent metastasis and lymphangiogenesis in human oral squamous cell carcinoma cells . Investigators demonstrated that the expression of WISP1 in HNSCC was significantly higher compared to normal tissue, suggesting that WISP1 expression might correlate with tumour progression .…”

“…40 The protein might be a potential target to prevent metastasis and lymphangiogenesis in human oral squamous cell carcinoma cells. 21 Investigators demonstrated that the expression of WISP1 in HNSCC was significantly higher compared to normal tissue, suggesting that WISP1 expression might correlate with tumour progression. 41 In a large study by Van Kempen et al comprising a cohort of oral and oropharyngeal cancers with known HPV status, CNAs and survival, WISP1 turned out to be a predictor for worse disease-free survival in oral and oropharyngeal squamous cell carcinoma, independent of HPV status.…”

“…19,20 There is an association between WISP1 and migration/angiogenesis in human oral squamous cell carcinoma cells, and HNSCC patients show higher expression of WISP1. 21 Our laboratory recently demonstrated that WISP1 was positively expressed in squamous cell salivary gland tumours. 22 However, the prognostic impact of WISP1 expression in HNSCC remains to be elucidated.…”

CCL5 promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-507 in human chondrosarcoma cells

“…After trypsinization, sections were blocked by incubation in 3% FBS in PBS. The primary antibody anti-human CCL5, VEGF-C or LYVE-1 was applied to the slides at a dilution from 1:50 to 1:150 and incubated at 4°C overnight [45]. After the slides were washed 3 times with PBS, the samples were treated with the secondary antibody at a dilution of 1:100.…”

MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

“…Our previous work revealed that miR-323a-3p, miR-433 and miR-409 transcribed from this cluster acted as tumor suppressors [16][17][18]. miR-300, belonging to the DLK1-DIO3 miRNA cluster, was previously reported to be associated with human osteosarcoma, pancreatic cancer, non-small cell lung cancer, glioblastoma, and oral squamous cell carcinoma [20][21][22][23][24]. However, to the best of our knowledge, the role miR-300 in BCa and its mechanism remains unresolved.…”