J Cancer 2019; 10(10):2220-2228. doi:10.7150/jca.28261
Tropomyosin-1 Functions as a Tumor Suppressor with Respect to Cell Proliferation, Angiogenesis and Metastasis in Renal Cell Carcinoma
Department of Urology, the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, Jilin, China.
*These authors contributed equally to this work.
Background: Tropomyosin-1 (TPM1) has long been known to be an actin-binding cytoskeletal protein. Multiple recent studies have revealed that TPM1 is down-regulated in various malignant tumors, including renal cell carcinoma (RCC).
Methods: To further verify its role in RCC, transfection of a reconstructed plasmid was used to bi-directionally regulate TPM1 levels. A colony formation assay, tube formation assay and invasion assay were adopted to assess cell proliferation, angiogenesis and metastasis, respectively, in the 786-O and ACHN cell lines. The xenograft tumor sizes were measured, and the microvessel density (MVD) was quantified. Western blot and immunohistochemistry (IHC) were used to detect key proteins involved in these processes.
Results: The colony formation assay and xenograft tumor models illustrated that TPM1 up-regulation inhibited RCC cell proliferation. The tube formation assay and detection of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) in xenografts revealed that TPM1 up-regulation inhibited angiogenesis in RCC. The invasion assay and detection of the E-cadherin and matrix metalloproteinases 9 (MMP-9) levels in xenografts demonstrated that TPM1 up-regulation inhibited tumor metastasis in RCC. Opposing effects were absent in TPM1 down-regulation models.
Conclusions: TPM1 functions as a tumor suppressor with respect to cell proliferation, angiogenesis and metastasis in RCC, suggesting that it is a potential therapeutic target for advanced RCC.
Keywords: Renal cell carcinoma, Tropomyosin-1, Cell Proliferation, Angiogenesis, Metastasis
Wang J, Tang C, Yang C, Zheng Q, Hou Y. Tropomyosin-1 Functions as a Tumor Suppressor with Respect to Cell Proliferation, Angiogenesis and Metastasis in Renal Cell Carcinoma. J Cancer 2019; 10(10):2220-2228. doi:10.7150/jca.28261. Available from http://www.jcancer.org/v10p2220.htm