Runx2 expression: A mesenchymal stem marker for cancer

Abstract

The transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically-expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment. However, studies evaluating this gene as a cancer marker are lacking. In the present study, Runx2 expression was analysed in 11 different cancer cell lines not derived from bone tumour. In addition, the presence of Runx2-related cell-free RNA was examined in the peripheral blood of 41 patients affected by different forms of tumours. The results demonstrated high expression levels of Runx2 in the cancer cell lines and identified the presence of Runx2-related cell-free RNA in the peripheral blood of patients with cancer. As compared with normal individuals, the expression level was increased by 14.2-fold in patients with bone metastases and by 4.01-fold in patients without metastases. The results of the present study therefore opens up the possibility to exploit Runx2 expression as a cancer biomarker allowing the use of minimally invasive approaches for diagnosis and follow-up.

Keywords: Runx2; cancer; cell-free RNA; epithelial-mesenchymal transition; gene expression.

Figure 1.

Runx2 mRNA fold expression in ACs and Ss of cancer cell lines. (A) All cell lines expressed Runx2 mRNA and (B) immunoblotting demonstrated that the ACs also expressed Runx2 protein. Runx2, runt-related transcription factor 2; ACs, adherent cells; Ss, supernatants.

Figure 2.

Runx2 expression in patients with cancer. (A) Circulating Runx2 mRNA in CPs was higher than in NDs (*P<0.01), and (B) patients with M expressed higher levels of Runx2 (*P<0.01) than NM patients with respect to NDs (^$P<0.05). Runx2, runt-related transcription factor 2; CP, cancer patients; NDs, normal donors; M, bone metastases; NM, non-metastatic.