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Review
. 2020 Sep 4;39(1):178.
doi: 10.1186/s13046-020-01685-w.

The role of extracelluar matrix in osteosarcoma progression and metastasis

Juncheng Cui  1   2 , Dylan Dean  2 , Francis J Hornicek  2 , Zhiwei Chen  3 , Zhenfeng Duan  4
Affiliations
Review

The role of extracelluar matrix in osteosarcoma progression and metastasis

Juncheng Cui et al. J Exp Clin Cancer Res. .

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; Metastasis; Osteosarcoma; Prognostic biomarker; Therapeutic target.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Fig. 1
Fig. 1
ECM changes in OS progression and metastasis. The primary components of ECM in normal bone are significantly changed in osteosarcoma (OS). Due to activated fibroblasts, cancer cells, collagen deposition, fibronectin, and other ECM components, ECM production is dramatically increased which results in a stiffer stroma and more aggressive phenotype. The basement membrane surrounding the primary tumor site is broken down by ECM remodeling enzymes allowing for OS cells from the primary tumor to undergo hematogenous spread where they frequently seed the lung
Fig. 2
Fig. 2
Schematic of signaling pathways involved the ECM remodeling in OS. The ECM is dynamically remodeled by multiple proteases and signaling pathways. In OS, MMP-2, MMP-9, and MMP-13 function via PI3K/Akt and ERK associated signaling pathways. Heparanase also participates in ECM remodeling, as it cleaves the ECM by heparan sulfate degradation, thus promoting OS cell invasion and metastasis
See this image and copyright information in PMC

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