Clinicopathological significance of glucose transporter protein-1 overexpression in human osteosarcoma

Abstract

Abstract. Although previous studies have demonstrated thatGlut-1 is the predominant glucose transporter, is significantly overexpressed in various types of tumor and is correlated with poor prognosis, the potential function and clinical value of Glut-1 expression in osteosarcoma remains largely unclear. In particular, the prospective associations between Glut-1 expression levels and clinicopathological factors remains to be elucidated. In the present study, immunohistochemistry was performed to detect Glut-1 protein expression in 51 paired osteosarcoma specimens and adjacent non-cancerous tissues, and reverse transcription-quantitative polymerase chain reaction analysis was performed to examine Glut-1 mRNA expression levels in 6 pairs of these tissues. Statistical analyses were conducted to determine the associations between Glut-1 expression and various clinicopathological parameters. Glut-1 protein was revealed to be overexpressed in 38 (74.5%) osteosarcoma tissues, but only in 6 (11.8%) adjacent non-cancerous tissues. Glut-1 mRNA levels were also upregulated in osteosarcoma tissues compared with adjacent non-cancerous tissues. While there were no clear statistical relationships between Glut-1 expression and patient sex, resection, tumor location, size, T stage and adjuvant treatment, Glut-1 expression levels were significantly associated with age, tumor-node-metastasis stage, lymph node metastasis and survival. The median survival time in patients with low Glut-1 expression levels was longer than in patients with a high expression level. Glut-1 was significantly overexpressed in osteosarcoma tissues, and Glut-1 expression was associated with clinicopathological factors which upregulate the invasion and metastasis of osteosarcoma, and may be a potential predictor of survival in patients with osteosarcoma.

Uptake of fluorescent d- and l-glucose analogues, 2-NBDG and 2-NBDLG, into human osteosarcoma U2OS cells in a phloretin-inhibitable manner

“…Consistent to the above notion, previous studies have shown that osteosarcoma cells including U2OS cells express GLUTs [31][32][33][34]. 2-NBDG uptake has also been reported in some osteosarcoma cells [33,35].…”

CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma

“…Osteosarcoma is the most commonly diagnosed primary malignant bone tumor, and can lead to tumor-related mortality among children and adolescents (1). Osteosarcoma is the most common form of bone and soft tissue malignant tumor, and is characterized by high tumor cell proliferation, high mortality and rapid metastasis (2). Unfortunately, the prognosis of patients with metastatic osteosarcoma remains poor (3).…”

Immunohistochemical Characterisation of GLUT1, MMP3 and NRF2 in Osteosarcoma

“…In canine OSA, a study of 44 canine osteosarcoma specimens showed 61% positive GLUT1 staining but no significant correlation was identified between GLUT1 and disease-free interval ( 51 ). Interestingly, Petty and colleagues also showed a subset of canine OSA with no or low GLUT1 staining as was seen in human OSA ( 44 ). Our findings of GLUT1 in OSA indicated that every specimen had some degree of positive immunostaining, however this varied between patients.…”

“…In human OSA, higher expression of SLCA1I correlated with a poor prognosis, shorter disease-free interval and increased angiogenesis ( 47 ). GLUT1 staining was previously identified in 74% of human OSA specimens and linked with increased tumor volume and metastatic potential, as well as increased recurrence rate ( 44 ).…”

“…Here we investigated three cancer promoting proteins that have been shown to be up regulated at the gene level in canine OSA compared to normal bone tissue ( 16 ). Indeed the importance of GLUT-1 ( 37 , 44 ), MMP3 ( 36 , 37 ) and NRF2 ( 45 ) is well established in human OSA. More recently a study used single cell RNAseq to investigate the cellular heterogeneity within human osteosarcoma specimens and identified MMP-3 as one of the top differentially expressed genes in OSA specimens ( 40 ).…”