Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma.

Zhe-Xiang Wang,Shao-Chun Ren,Jing Ren,Zi-Song Chang,Pierfrancesco Franco

doi:10.1155/2020/7102757

Abstract

Background Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease. In recent years, the involvement of KIF2A in cancer progression has been widely revealed; however, its potential effect on osteosarcoma development remains unknown. This study is to assess the KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. Methods Immunohistochemical (IHC) assays were conducted to evaluate the expression levels of KIF2A in a total of 74 samples of osteosarcoma tissues and adjacent nontumor tissues. According to the staining intensity in tumor tissues, patients were divided into highly expressed and low expression KIF2A groups. The possible links between the KIF2A expression and the clinical pathological features were explored and analyzed, and the effects of KIF2A on osteosarcoma cell proliferation, migration, and invasion were detected through colony formation assay, MTT assay, wound closure assay, and transwell assay, respectively. The effects of KIF2A on tumor growth and metastasis were detected by the use of animal models. Results KIF2A was highly expressed in human osteosarcoma tissues. Meanwhile, KIF2A was obviously correlated to the tumor size (P = 0.001∗) and clinical stage (P = 0.014∗) of osteosarcoma patients. Our results also revealed that the ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Conclusions We investigated the involvement of KIF2A in the development and metastasis of osteosarcoma and therefore thought KIF2A as a promising therapeutic target for osteosarcoma treatment.

Highlights

Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease
We further found that Kinesin family member 2A (KIF2A) knockdown dramatically restrained osteosarcoma cell proliferation, migration, and invasion and suppressed tumor growth and metastasis in mice
To assess the possible role of KIF2A in the development and metastasis of osteosarcoma, the expression levels of KIF2A in osteosarcoma tissues of patients who underwent surgical resection were detected through IHC assays

Summary

Introduction

Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease. The involvement of KIF2A in cancer progression has been widely revealed; its potential effect on osteosarcoma development remains unknown. This study is to assess the KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. KIF2A was highly expressed in human osteosarcoma tissues. Our results revealed that the ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Osteosarcoma (OS) is one of the most common human bone malignancies, with high morbidity and mortality among patients aged 10-20 years old [1, 2]. Targeted therapy for osteosarcoma has shown great promise, and novel therapeutic targets are still urgently needed to combat this disease [9, 10]

Results

Discussion

Conclusion