Osteosarcoma progression is associated with increased nuclear levels and transcriptional activity of activated β-Catenin

Abstract

Osteosarcoma (OS) is an aggressive primary bone malignancy that has peak incidence in children and young adults <25 years of age. Despite current multimodal treatments, no significant change in patient outcome has been observed in two decades. Presently, there is a lack of established, reliable baseline prognostic markers for aggressive OS, other than extent and site of disease involvement. The canonical Wnt/β-catenin pathway controls multiple cellular processes, and is known to be a critical pathway in OS progression. This pathway regulates cellular levels of β-catenin, which is a significant player in the oncogenesis and progression of many cancers. We investigated the relationship between β-catenin, more specifically, the transcriptionally active form of β-catenin, Activated β-Catenin (ABC), and OS progression. Using an in vitro model, we observed that cellular/nuclear ABC levels, but not cellular/nuclear β-catenin levels, increase with the degree of aggressiveness in OS. Our results demonstrate a strong association between nuclear-ABC levels and aggressive OS in vitro . Furthermore, we observed significant correlation between positive nuclear-ABC and patient age and tumor stage. Our results support the potential use of ABC as a predictive marker for risk stratification in OS.

A Spheroid Model of Early and Late‐Stage Osteosarcoma Mimicking the Divergent Relationship between Tumor Elimination and Bone Regeneration

“…H&E staining showed the presence of Extracellular Matrix (ECM) within both models. Finally, there was a significant increase in gene expression for known prognostic markers Matrix metallopeptidase 9 (MMP9), [23c,24] SRY-Box Transcription Factor 9 (SOX9), [25] RUNX Family Transcription Factor 2 (RUNX2), [26] and 𝛽-catenin [27] in the late-stage model over the early-stage further replicating trends seen clinically (Figure 1I-N).…”

LINC01128 regulates the development of osteosarcoma by sponging miR‐299‐3p to mediate MMP2 expression and activating Wnt/β‐catenin signalling pathway

“…A previous study demonstrated that OS progression is associated with the transcriptional activity of activated β-catenin. 23 Besides, some studies have also shown that MMP2 is closely associated with the Wnt/β-catenin signalling pathway. [24][25][26] This study Recently, increasing number of studies have reported the pivotal roles of lncRNAs in the occurrence and development of OS.…”

Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells

“…We demonstrated LM7 metastatic potential by gelatin zymography assessing MMP2 and MMP9 activity. MMP2 and MMP9 have been previously reported to be directly associated with high grade OS and metastatic potential [29]. We demonstrated that the CM from LM7 had MMP2-gelatinase activity, while SAOS2 CM did not show this activity.…”