Restoration of S100A4 expression enhances invasive and metastatic potentials of COLO16 cutaneous squamous cancer cells.

Abstract

BACKGROUND:

S100A4 promotes cancer metastasis but is frequently silenced in human cutaneous squamous cell carcinomas/c-SCCs due to DNA methylation, which may explain the less metastasized property of c-SCCs.

OBJECTIVE:

This study aims to check 1) whether the metastatic potential of S100A4-negative human c-SCC cells could be enhanced when S100A4 expression is restored in COLO16 c-SCC cells with S100A4 methylation and 2) the correlation of S100A4 expression and the differentiation grades and invasiveness of human c-SCC tumors.

METHODS:

The motility and invasion of parent and transfected COLO16 cells are examined by the use of 24-well modified Boyden chambers, scratched wound healing assay and nude mouse transplantation tumor model. Meanwhile, the correlation of S100A4 expression with growth patterns and grade of differentiation of c-SCC surgical specimens are analyzed.

RESULTS:

S100A4 expression is successfully restored in COLO16 cells after plasmid lipofectamine transfection. Transwell and scratched wound healing assays shows that the invasion and migration activities of S100A4-expressing transfectants are higher than that of parent COLO16 cells. Subcutaneous and foot pad c-SCC models are established by injecting 5 × 10<formula>^{6}</formula>/100~l parental and S100A4-expressing COLO16 cells to BALB/c-nu/nude mice, respectively. Histological examination confirms the differences of invasiveness between the parent cells and the transfectants. Regional lymph node metastases are found only in the mice bearing S100A4-expressing tumors. S100A4 expression levels and frequencies are significantly different (P< 0.001) between the well and the poorly differentiated c-SCCs and closely correlated with tumor invasion (P< 0.05).

CONCLUSIONS:

S100A4 confers invasive and metastatic potentials on human c-SCCs. The low incidence of metastasis of c-SCCs, especially the well differentiated ones, might be due to the infrequent S100A4 expression. S100A4 can be regarded as a negative prognostic biomarker or a metastasis-risk factor of human c-SCCs.

• Authors: Li-Jun Yu, Yan Li, Cong Li, Hong Li, Mo-Li Wu, Zhi-Li Liu, Qing-You Kong, Xiao-Yan Chen, Xiao-Yu Liu, Li-Jia An, Jia Liu
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 14 Issue 5 Pg. 325-33 ( 2014) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 25171474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• S100 Calcium-Binding Protein A4
• S100 Proteins
• S100A4 protein, human

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, pathology)
• Cell Differentiation (genetics)
• Cell Line, Tumor
• Female
• Humans
• Lymphatic Metastasis (genetics, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Transplantation (pathology)
• S100 Calcium-Binding Protein A4
• S100 Proteins (genetics)
• Skin Neoplasms (genetics, pathology)
• Transfection