The role of extracelluar matrix in osteosarcoma progression and metastasis
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(2020) 39:178
REVIEW
Open Access
The role of extracelluar matrix in osteosarcoma progression and metastasis Juncheng Cui1,2, Dylan Dean2, Francis J. Hornicek2, Zhiwei Chen1* and Zhenfeng Duan2*
Abstract Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS. Keywords: Extracellular matrix, Osteosarcoma, Metastasis, Prognostic biomarker, Therapeutic target
Background Osteosarcoma (OS) is the most common primary bone malignancy and disproportionately affects those in childhood and adolescence [1]. Before the widespread use of chemotherapy in the 1970s, surgical resection was the primary treatment modality available to OS patients [2]. Adjuvant chemotherapy has since dramatically improved the prognosis for OS patients, with the five-year survival rate increased from 20% to approximately 55 to 70% in patients with localized disease [3, 4]. However, in cases of metastatic lesions, the five-year survival rate remains dismal at less than 20% [5]. Targeting and preventing metastasis has thus been a significant obstacle in OS treatment, and recent publications have highlighted * Correspondence: [email protected]; [email protected] 1 Department of Orthopedic Surgery, The First Affiliated Hospital of University of South China, 69 Chuanshan Road, Hengyang 421001, Hunan, China 2 Department of Orthopedic Surgery, Sarcoma Biology Laboratory, David Geffen School of Medicine at UCLA, 615 Charles E. Young Dr. South, Los Angeles, CA 90095, USA
various novel treatment strategies to that end. The dysregulation and aberrant remodeling of extracellular matrix (ECM) has gained considerable attention for its promise in pathogenic targeting and predictive value. Very recently, the tumor microenvironment (TME) has gained prominence outside of its traditional role of cellular support as a veritable co
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