Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction

In the present study, we searched for mutant PTEN
transcripts in aggressive rheumatoid arthritis synovial fibroblasts (RA-SF) and
studied the expression of PTEN in RA. By automated sequencing, no evidence for
the presence of mutant PTEN transcripts was found. However, in
situ hybridization on RA synovium revealed a distinct expression pattern
of PTEN, with negligible staining in the lining layer but abundant expression
in the sublining. Normal synovial tissue exhibited homogeneous staining for
PTEN. In cultured RA-SF, only 40% expressed PTEN. Co-implantation of RA-SF and
normal human cartilage into severe combined immunodeficiency (SCID) mice showed
only limited expression of PTEN, with no staining in those cells
aggressively invading the cartilage. Although PTEN is not genetically altered
in RA, these findings suggest that a lack of PTEN expression may constitute a
characteristic feature of activated RA-SF in the lining, and may thereby
contribute to the invasive behaviour of RA-SF by maintaining their aggressive
phenotype at sites of cartilage destruction.