Original Article

Overexpression of S100A1 in Osteosarcoma Inhibits Tumor Proliferation and Progression

Abstract

Background: Osteosarcoma is the most common primary malignant tumor of bone. Abnormal expression of S100A1 protein is closely related to the occurrence and development of malignant tumors. However, S100A1 in osteosarcoma has not been studied.

Methods: All osteosarcoma tissues were collected from patients who received surgical therapy at the Affiliated Hospital of Inner Mongolia Medical University, China in 2020. QRT-PCR and western blot assays were used to detect the expression of S100A1 in osteosarcoma tissues and cells. The negative effect of S100A1 on osteosarcoma cell growth was confirmed by vitro and vivo experiments.

Results: S100A1 inhibited the growth of osteosarcoma cells in vitro. Overexpression of S100A1 may inhibit the proliferation of osteosarcoma cells by preventing the activation of AKT signaling pathway by western blot assay. Finally, animal experiments confirmed that overexpression of S100A1 could inhibit the proliferation of osteosarcoma cells. Overexpression of S100A1 obtained better survival benefit in mice.

Conclusion: Our findings provided a new insight to the treatment of osteosarcoma. It also raised the possibility that S100A1 could be used in targeted therapies for osteosarcoma.

1. Ritter J, Bielack SS (2010). Osteosarcoma. Ann Oncol, 21 Suppl 7:vii320-5.
2. Sangle NA, Layfield LJ (2012). Telangiectatic osteosarcoma. Arch Pathol Lab Med, 136:572-6.
3. Simpson E, Brown HL (2018). Understanding osteosarcomas. JAAPA, 31:15-19.
4. Biazzo A, De Paolis M (2016). Multidisciplinary approach to osteosarcoma. Acta Orthop Belg, 82:690-698.
5. Bresnick AR, Weber DJ, Zimmer DB (2015). S100 proteins in cancer. Nat Rev Cancer, 15:96-109.
6. Lesniak W, Graczyk-Jarzynka A (2015). The S100 proteins in epidermis: Topology and function. Biochim Biophys Acta, 1850:2563-72.
7. Chen H, Xu C, Jin Q, Liu Z (2014). S100 protein family in human cancer. Am J Cancer Res, 4:89-115.
8. Gonzalez LL, Garrie K, Turner MD (2020). Role of S100 proteins in health and disease. Biochim Biophys Acta Mol Cell Res, 1867:118677.
9. Cmoch A, Groves P, Palczewska M, Pikula S (2012). S100A proteins in propagation of a calcium signal in norm and pathology. Postepy Biochem, 58:429-36.
10. Tian T, Li X, Hua Z, Ma J, Liu Z, Chen H, Cui Z (2017). S100A1 promotes cell proliferation and migration and is associated with lymph node metastasis in ovarian cancer. Discov Med, 23:235-245.
11. Mori Y, Mori D, Chung UI, et al (2014). S100A1 and S100B are dispensable for endochondral ossification during skeletal development. Biomed Res, 35:243-50.
12. Fan L, Liu B, Guo R, et al (2019). Elevated plasma S100A1 level is a risk factor for ST-segment elevation myocardial infarction and associated with post-infarction cardiac function. Int J Med Sci, 16:1171-1179.
13. Guo Q, Wang J, Cao Z, Tang Y, Feng C, Huang F (2018). Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma. Int J Oncol, 53:592-602.
14. Mokari-Yamchi A, Sharifi A, Kheirouri S (2018). Increased serum levels of S100A1, ZAG, and adiponectin in cachectic patients with COPD. Int J Chron Obstruct Pulmon Dis, 13:3157-3163.
15. Shorning BY, Dass MS, Smalley MJ, Pearson HB (2020). The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int J Mol Sci, 21(12):4507.
16. Li L, Tang P, Li S, et al (2017). Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy. Med Oncol, 34:180.
17. Xie Y, Shi X, Sheng K, et al (2019). PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review). Mol Med Rep, 19:783-791.
18. Su Y, Luo X, He BC, et al (2009). Establishment and characterization of a new highly metastatic human osteosarcoma cell line. Clin Exp Metastasis, 26:599-610.
19. Diaz-Romero J, Quintin A, Schoenholzer E, et al (2014). S100A1 and S100B expression patterns identify differentiation status of human articular chondrocytes. J Cell Physiol, 229:1106-17.
20. Diaz-Romero J, Nesic D (2017). S100A1 and S100B: Calcium Sensors at the Cross-Roads of Multiple Chondrogenic Pathways. J Cell Physiol, 232:1979-1987.
21. Sun B, Kekenes-Huskey PM (2020). Molecular Basis of S100A1 Activation and Target Regulation Within Physiological Cytosolic Ca(2+) Levels. Front Mol Biosci, 7:77.
22. Duarte-Costa S, Castro-Ferreira R, Neves JS, Leite-Moreira AF (2014). S100A1: a major player in cardiovascular performance. Physiol Res, 63:669-81.
23. Dowarha D, Chou RH, Yu C (2020). S100A1 blocks the interaction between p53 and mdm2 and decreases cell proliferation activity. PLoS One, 15:e0234152.
24. Ersahin T, Tuncbag N, Cetin-Atalay R (2015). The PI3K/AKT/mTOR interactive pathway. Mol Biosyst, 11:1946-54.
Files
IssueVol 51 No 12 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v51i12.11468
Keywords
S100A1 protein Osteosarcoma Proliferation Progression

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Xing W, Zhao Y, Lin L, Zhao Z, Yang M, Wang N, Cui S, Bai R, Zhao A. Overexpression of S100A1 in Osteosarcoma Inhibits Tumor Proliferation and Progression. Iran J Public Health. 2022;51(12):2773-2782.