LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients
| Autor: | Ju Han, Ping Xian Tan, Xian Biao Xie, Qing Lian Tang, Jing Wang, Bi Cheng Yong, Gang Huang, Qiao Su, Jing Nan Shen, Jin Chang Lu, Hong Wen Xu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Lung Neoplasms Cell Kaplan-Meier Estimate Mice SCID Metastasis law.invention Mice 0302 clinical medicine law Cell Movement Mice Inbred NOD Child Wnt Signaling Pathway RC254-282 Osteosarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Nuclear Proteins General Medicine Middle Aged WNT5A Survival Rate medicine.anatomical_structure 030220 oncology & carcinogenesis Heterografts musculoskeletal diseases Adult medicine.medical_specialty Leucine zipper Adolescent Bone Neoplasms Wnt-5a Protein 03 medical and health sciences Young Adult Internal medicine Cell Line Tumor medicine Animals Humans neoplasms Retrospective Studies business.industry Tumor Suppressor Proteins Cancer medicine.disease 030104 developmental biology Suppressor business |
| Zdroj: | Tumor Biology, Vol 39 (2017) |
| ISSN: | 1423-0380 |
| Popis: | Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan–Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan–Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas. |
| Databáze: | OpenAIRE |
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