TU8: TUMOUR SIZE AND INVASIVE CAPACITY IS ASSOCIATED WITH INCREASED RECK EXPRESSION IN SARCOMAS OF BONE

Abstract

The human RECK protein is often downregulated in cancer, which is thought to contribute to tumour progression. The role of RECK is not yet characterised in bone sarcomas. This study aims to determine the effects of increased human RECK protein expression in osteo-sarcoma and chondrosarcoma using cell invasion assays and tumour size on MRI.

The human osteosarcoma and chondrosarcoma cell lines (SaOS-2 and OUMS27 respectively) were cultured then transfected with either a plasmid containing the RECK gene, an empty vector, or not at all (control). Cells were incubated at 37 degrees within invasion chambers containing 75% matrigel. Cells invading the matrigel were counted after 3 days. Fifteen chondrosar-coma samples were stained using immunohistochemistry for the human RECK protein. RECK expression was determined to be positive or negative. MRI scans corresponding to tumour samples were viewed and the maximal tumour diameter out of all planes was manually determined with computer imaging software.

The SaOS-2 invasion assay demonstrated increased cell invasion in the RECK transfected group with an average of 502.3 invading cells, compared with 129.0 for the empty vector group (p=0.004) and 100.6 for the control group (p=0.001).

The OUMS-27 invasion assay also demonstrated increased cell invasion in RECK transfected cells with an average of 86.3 invading cells compared with 22.8 in the empty vector group (p=0.067) and 67.8 in the control group (p=0.17).

For MRI data, there were two distinct groups with roughly equal distributions of tumour grades. Group 1 had maximal tumour diameters of less than 70 mm, compared to group 2, being greater than 70mm (p=0.0006). In group 1 only 1/8 demonstrated RECK expression, while in group 2, 5/7 were RECK positive (p=0.041 Fisher exact test).

RECK overexpression in osteosarcoma and chondro-sarcoma cell lines appears to increase invasive capacity, and stands in contrast to RECK data in carcinomas. Furthermore, RECK expression in patient chondrosar-coma samples is associated with larger tumours. RECK may therefore function differently in sarcoma.