Department of Cell Biology and Genetics and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, China.
Shaanxi Key Laboratory of Brain Disorders and Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
Cancer Res Treat. 2021 Apr;53(2):576-583. doi: 10.4143/crt.2020.801. Epub 2020 Oct 29.
Bone destruction and pain caused by cancer is one of the most devastating complications of cancer patients with bone metastases, and it seriously affects the quality of patients' life. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule with increased expression in a variety of tumors. This study focused to clarify the specific function of EMMPRIN in bone metastasis of breast cancer.
Adenovirus with shRNA-EMMPRIN was transfected into MRMT-1 rat breast carcinoma cells, and the MRMT-1 cells with different expression levels of EMMPRIN were implanted into the bone marrow cavity of rat tibia. Next, the effect of down-regulation of EMMPRIN was evaluated as follows: bone damage was detected by X-ray radiological and tartrate-resistant acid phosphatase staining; the tumor burden was evaluated by hematoxylin and eosin staining; the test of pain-related behaviors was assessed used the bilateral paw withdrawal mechanical threshold; and the levels of secretory factors in tumor conditioned medium were determined by using enzyme-linked immunosorbent assay.
We found that down-regulation of EMMPRIN in tumor cells can simultaneously reduce tumor burden, relieve cancer-induced bone destruction and pain.
EMMPRIN is expected to be a therapeutic target for relieving bone metastasis of breast cancer and alleviating cancer-induced bone destruction and pain. The method of targeting EMMPRIN may be a promising strategy for the treatment of cancer in the future.
癌症引起的骨破坏和疼痛是癌症骨转移患者最具破坏性的并发症之一,严重影响患者的生活质量。细胞外基质金属蛋白酶诱导因子(EMMPRIN)是一种细胞黏附分子,在多种肿瘤中表达增加。本研究旨在阐明 EMMPRIN 在乳腺癌骨转移中的具体作用。
用 shRNA-EMMPRIN 转染腺病毒,将不同 EMMPRIN 表达水平的 MRMT-1 大鼠乳腺癌细胞植入大鼠胫骨骨髓腔。然后,通过以下方法评估下调 EMMPRIN 的效果:X 射线影像学和抗酒石酸酸性磷酸酶染色检测骨损伤;苏木精和伊红染色评估肿瘤负担;双侧足底撤回机械阈值测试评估疼痛相关行为;酶联免疫吸附试验测定肿瘤条件培养基中分泌因子的水平。
我们发现下调肿瘤细胞中的 EMMPRIN 可以同时减轻肿瘤负担、缓解癌症引起的骨破坏和疼痛。
EMMPRIN 有望成为缓解乳腺癌骨转移和减轻癌症引起的骨破坏和疼痛的治疗靶点。靶向 EMMPRIN 的方法可能是未来癌症治疗的一种有前途的策略。