Osteosarcoma, a prevalent primary malignant bone tumor, predominantly affects both elderly and adolescent populations and usually has an unfavorable prognosis. The specific mechanisms underlying its invasive progression remain unclear. The tumor microenvironment includes not only cancer cells but also bone-related cells, immune cells, tumor-associated nerve cells, and cell-secreted factors. The cooperative and competitive interactions among these cellular components contribute to the proliferation, progression, metastasis, and immune evasion of osteosarcoma. Alterations in bone-related cells, resulting from oncogenic changes, can rapidly increase bone density or aggravate bone loss, thereby promoting the survival of osteosarcoma cells. During the progression of osteosarcoma, genetic alterations in tumor cells lead to changes in extracellular matrix components, influencing the variation in cell-secreted factors, promoting immunosuppression within the tumor microenvironment, and consequently affecting tumor proliferation and progression. This review summarizes the roles of tumor microenvironment components in the pathogenesis of osteosarcoma and discusses existing therapeutic targets. The findings suggest potential research directions for further investigation of osteosarcoma, provide novel insights into the development of osteosarcoma, and may guide the development of more effective anti-tumor strategies.

The long non-coding RNA taurine up-regulated gene 1 (TUG1) has been reported to be involved in various cancers, but its role in chondrosarcoma (CHS) remains a mystery. This research aimed to examine the function of TUG1 in CHS. We found that TUG1 expression was elevated in CHS. Functional assays demonstrated that TUG1 had a crucial role in the CHS cell progression. Mechanistically, TUG1 recruited ALYREF to maintain the stabilization of enhancer of zest homolog 2 (EZH2) mRNA and expression of H3K27me3, repressing the transcription of the tumor-suppressor gene CPEB1. Additionally, exosomal TUG1 enhanced the polarization of M2 tumor-associated macrophages, which increased the proliferation and metastasis of CHS. Taken together, this study revealed the oncogenic role of TUG1 in CHS and its interactions with the downstream regulatory axis, offering novel insights into the tumorigenic mechanism of CHS.

Osteosarcoma (OS), frequently observed in children and adolescents, is one of the most common primary malignant tumors of the bone known to be associated with a high capacity for invasion and metastasis. The incidence of osteosarcoma in children and adolescents is growing annually, although improvements in survival remain limited. With the clinical application of neoadjuvant chemotherapy, chemotherapy combined with limb-preserving surgery has gained momentum as a major intervention. However, certain patients with OS experience treatment failure owing to chemoradiotherapy resistance or metastasis. Nuclear factor E2-related factor 2 (Nrf2), a key antioxidant factor in organisms, plays a crucial role in maintaining cellular physiological homeostasis; however, its overactivation in cancer cells restricts reactive oxygen species production, promotes DNA repair and drug efflux, and ultimately leads to chemoradiotherapy resistance. Recent studies have also identified the functions of Nrf2 beyond its antioxidative function, including the promotion of proliferation, metastasis, and regulation of metabolism. The current review describes the multiple mechanisms of chemoradiotherapy resistance in OS and the substantial role of Nrf2 in the signaling regulatory network to elucidate the function of Nrf2 in promoting OS chemoradiotherapy resistance and formulating relevant therapeutic strategies.