The role of extracelluar matrix in osteosarcoma progression and metastasis

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.

Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis

“…Adjuvant chemotherapy has been demonstrated to greatly improve the prognosis for patients with osteosarcoma by increasing the five-year survival rate from 20% to approximately 55–70% [ 2 ]. However, the five-year survival rate remains dismal at less than 20% in patients with osteosarcoma and metastatic lesions [ 3 ]. Therefore, the development of novel treatment strategies that target and prevent metastasis is urgently required to promote patient survival.…”

The inhibitory effect of CTAB on human osteosarcoma through the PI3K/AKT signaling pathway

“…Our data suggest that CTAB significantly inhibits the proliferation of osteosarcoma cells, leading to G1 arrest, suppresses metastasis and induces apoptosis. One of the clinical features of osteosarcoma is the tendency to form metastatic lesions, and the degradation of extracellular matrix is an essential step in cancer invasion and metastasis (22,23). Previous findings have showed that CTAB can selectively inhibit the proliferation of prostate cancer cells and markedly decrease the invasion of DU-145 cells in the collagen matrix (24).…”

Global Characterization of Immune Infiltration in Clear Cell Renal Cell Carcinoma

“…Previous research has shown that extracellular matrix remodeling is the hallmark of tumor progression. 43 Its transition promotes tumor metastasis but also acts as a physical barrier to inhibit immune cell infiltration. 44 In addition, collagen, the major component of the extracellular matrix, can induce exhaustion of CD8 T cells.…”