Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors
Autor: | Yuanlong He, Xian Jiang, Xiangjun Xie, Haiquan Qiao, Xueying Sun, Linhao Li, Xuesong Dong, Yuqiang Gao, Fangyu Xie, Qian Zhang |
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Jazyk: | angličtina |
Předmět: |
Male
0301 basic medicine Cancer Research Cell signaling Pathology medicine.medical_specialty Proliferation Nerve Tissue Proteins Biology medicine.disease_cause Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Stomach Neoplasms Cell Line Tumor Cellular signaling Neuropilin 1 medicine Animals Humans Cell Proliferation Cell growth Research Cancer Prognosis medicine.disease Survival Analysis Neuropilin-1 Gene Expression Regulation Neoplastic C-Reactive Protein 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Female Clinicopathology Signal transduction Gastric cancer Carcinogenesis Neoplasm Transplantation Signal Transduction |
Zdroj: | Journal of Experimental & Clinical Cancer Research : CR |
ISSN: | 1756-9966 |
DOI: | 10.1186/s13046-016-0291-5 |
Popis: | Background Neuropilin-1 (NRP-1) is a transmembrane glycoprotein participating in the growth and metastasis of cancer cells as multifunctional co-receptors by interacting with the signaling pathways. However, its role in gastric cancer has not yet been clarified. This study aims to investigate whether NRP-1 expression is associated with the clinicopathology of gastric cancer, and involved in the growth and metastasis of gastric cancer cells. Methods NRP-1 expression in clinical gastric cancer specimens was examined by immunohistochemistry and its association with clinicopathology analyzed. The expression of NRP-1 in a panel of human gastric cancer cells was examined by real-time RT-PCR and immunoblotting. Stable transfectants depleted of NRP-1, termed MGC-803-NRPlow, were generated from MGC-803 cells. Cell proliferation was analyzed by the Cell Counting Kit-8 and Bromodeoxyuridine incorporation assays, and migrating ability analyzed by migration assays. The xenograft model was used to assess the effects of NRP-1 depletion on tumorigenesis, growth, metastasis and therapeutic potentials. The role of NRP-1 as co-receptors in the signaling pathways stimulated by ligands was examined. The key molecules involved in cell proliferation, migration and related signaling pathways were detected by immunoblotting. Results Gastric cancer tissues expressed higher levels of NRP-1 compared to normal gastric mucosa. Its expression correlated with clinical staging, tumor differentiation and pathological types. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest in the G1/S phase by upregulating p27, and downregulating cyclin E and cyclin-dependent kinase 2. NRP-1 depletion reduced the ability of cells to migrate by inhibiting the phosphorylation of focal adhesion kinase. NRP-1 depletion suppressed tumorigenesis, tumor growth and lung metastasis by inhibiting cell proliferation and tumor angiogenesis in situ. Therapeutic NRP-1 shRNA inhibited the growth of established BGC823 tumors. Depletion of NRP-1 inhibited the activation of VEGF/VEGFR2, EGF/EGFR and HGF/c-Met pathways stimulated by respective recombinant human VEGF-165, EGF and HGF proteins. Conclusions The present results indicate that NRP-1 may be a potentially valuable biomarker and therapeutic target for gastric cancer. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0291-5) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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