Upregulation of PLOD2 promotes invasion and metastasis of osteosarcoma cells
10.3760/cma.j.issn.0253-3766.2019.06.007
- VernacularTitle: 赖氨酸羟化酶2在骨肉瘤组织中的表达及其对骨肉瘤细胞迁移和侵袭的影响
- Author:
Fei CAO
1
;
Xiaohong KANG
2
;
Yanhui CUI
2
;
Ying WANG
2
;
Kelei ZHAO
2
;
Yanan WANG
2
;
Weizheng KOU
2
;
Zhanhui MIAO
2
;
Xiangjun CAO
1
Author Information
1. Department of Orthopedics, Ping Ding Shan First People′s Hospital, Pingdingshan 467000, China
2. Department of Oncology, the first Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
- Publication Type:Journal Article
- Keywords:
PLOD2;
Osteosarcoma;
Invasion;
Metastasis;
Signal pathway
- From:
Chinese Journal of Oncology
2019;41(6):435-440
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2.
Methods:The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting.
Results:The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells.
Conclusions:Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.
