Potential role of S-adenosylmethionine in osteosarcoma development

Abstract

The metastatic form of osteosarcoma is a life threatening one since it metastasizes to the lungs. The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease. In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression. As evidence of tumor suppression, the SAM-treated mouse tissue was analyzed histologically, which exemplifies the control that SAM has over abnormal cell proliferation, especially on primary osteosarcoma, but it lacks positive effects on metastatic osteosarcoma. At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP. The data suggest that the administration of SAM has a positive role in treating primary osteosarcoma, but it has no role in suppressing metastatic osteosarcoma. The decreased expression of Sox2 together with upregulation of TCTP following SAM administration indicates that SAM has a control over primary osteosarcoma.

Keywords: BALB/c mouse; K7M2 cells; S-adenosylmethionine; Sox2; TCTP.

Figure 1

Histological characteristics of normal and osteosarcoma tissues. Notes: (A) Histological section of normal bone tissue of a mouse showing uniform arrangement of cells. (B) Primary osteosarcoma tissue with abnormal mass of cells. (C) Metastatic osteosarcoma tissue showing irregular cells that are enlarged in size when compared to normal cells. (D) Primary osteosarcoma tissue treated with SAM showing reversion in cellular pattern. (E) Metastatic osteosarcoma tissue treated with SAM showing no changes in cellular pattern. Scale bar: 100 µm. Abbreviation: SAM, S-adenosylmethionine.

Figure 2

Analysis of Sox2 expression in normal and osteosarcoma tissues. Notes: (A) Sox2 expression in normal bone tissue of a mouse. (B) Sox2 expression in primary osteosarcoma tissue. (C) Sox2 expression in metastatic osteosarcoma tissue. (D) Sox2 expression in SAM-treated primary osteosarcoma tissue. (E) Sox2 expression in SAM-treated metastatic osteosarcoma tissue. Scale bar: 100 µm. Abbreviation: SAM, S-adenosylmethionine.

Figure 3

Analysis of TCTP expression in normal and osteosarcoma tissues. Notes: (A) TCTP expression in normal bone tissue of a mouse. (B) TCTP expression in primary osteosarcoma tissue. (C) TCTP expression in metastatic osteosarcoma tissue. (D) Increased TCTP expression in SAM-treated primary osteosarcoma tissue. (E) TCTP expression in SAM-treated metastatic osteosarcoma tissue. Scale bar: 100 µm. Abbreviation: SAM, S-adenosylmethionine.

Figure 4

Western blotting analysis of Sox2 and TCTP expression. Notes: The protein samples were prepared from SAM-treated osteosarcoma tissue along with various controls and subjected to Western blotting analysis and then stained with anti-Sox2 antibody and anti-TCTP antibody. Lane 1 shows Sox2 and TCTP expression in normal bone tissue samples of mice. Lane 2 represents Sox2 and TCTP expression in primary osteosarcoma tissue samples. Lane 3 represents Sox2 and TCTP expression in metastatic osteosarcoma tissue samples. Lane 4 shows Sox2 and TCTP expression in SAM-treated primary osteosarcoma tissue samples. Lane 5 represents Sox2 and TCTP expression in SAM-treated metastatic osteosarcoma tissue samples. Tubulin was used as a loading control. Abbreviation: SAM, S-adenosylmethionine.