MUC 15 Promotes Osteosarcoma Cell Proliferation, Migration and Invasion through Livin, MMP-2/MMP-9 and Wnt/β-Catenin Signal Pathway

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Abstract

Objective: To investigate the high expression of MUC15 in promoting proliferation, migration and invasion in osteosarcoma (OS) cell and its potential mechanism.

Methods: The expressions of MUC15 in OS patients were analyzed from GEO Datasets, tumor cell lines and clinical samples. The roles of MUC15 in OS were explored by CCK-8, flow cytometry, transwell and western blot assay, respectively.

Results: MUC15 was highly expressed in osteosarcoma, and there was a significant negative correlation between MUC15 and the prognosis. Knockdown of MUC15 in HOS and U-2OS could promote tumor cell apoptosis, down-regulate the expression of MMP2/9, reduce the epithelial interstitial transition and silence the Wnt/b-Catenin signal pathway.

Conclusion: The high-expression of MUC15 promotes the proliferation, migration and invasion of osteosarcoma through anti-apoptosis, increasing the invasive ability by epithelial interstitial transition, and activating the Wnt/b-Catenin signal pathway.

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Most cited references 29

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Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.

Michael Isakoff, Stefan S. Bielack, Paul S. Meltzer … (2015)

Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor.

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Update on Survival in Osteosarcoma.

Megan E Anderson (2016)

Osteosarcoma is the most common primary bone malignancy in children. Treatment has evolved to include systemic chemotherapy and local control surgery. Although survival improved initially in a drastic fashion with this approach, recent decades have seen little to no further gains in this area. Limb salvage surgery evolved with effective chemotherapy and advances in imaging, and continues to improve in the recent era. This article serves as a review of survival in high-grade osteosarcoma: prognostic factors, advances in chemotherapy and surgery, late effects of chemotherapy and surgery in survivors, and future directions.

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Current and future therapeutic approaches for osteosarcoma.

Jonathan D. Gill, Valerae O. Lewis, Richard Gorlick … (2018)

Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%. Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise. Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2021

Publication date (Electronic): 1 January 2021

Volume: 12

Issue: 2

Pages: 467-473

Affiliations

[1 ]Suzhou Ninth People's Hospital, Suzhou, Jiangsu 215200, China.

[2 ]Danyang People's Hospital of Jiangsu Province, Danyang, Jiangsu 212300, China.

[3 ]Danyang Hospital Affiliated to Nantong University, Danyang, Jiangsu 212300, China.

[4 ]Department of Assay Development, TOT BIOPHARM co., LTD, Suzhou, Jiangsu 215024, China.

Author notes

✉ Corresponding authors: Central Laboratory, Danyang, Danyang People's Hospital of Jiangsu Province, Jiangsu 212300, China. E-mail: zhangshaoru@ 123456126.com (Shaoru Zhang), lihuiwang@ 123456nju.edu.cn (Lihui Wang).

#These authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: jcav12p0467

DOI: 10.7150/jca.49641

PMC ID: 7739004

PubMed ID: 33391443

SO-VID: 5bbcd06c-9682-4f54-baaa-d2d405b29507

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

MUC 15 Promotes Osteosarcoma Cell Proliferation, Migration and Invasion through Livin, MMP-2/MMP-9 and Wnt/β-Catenin Signal Pathway

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Karger: Oncology

Most cited references 29

Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.

Update on Survival in Osteosarcoma.

Current and future therapeutic approaches for osteosarcoma.

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