Osteosarcoma (OS) is a highly malignant primary skeletal
tumor with a striking tendency to rapidly destroy the surrounding bone and metastasize, since
metastases are frequently present at clinical onset. The basis for the aggressiveness of this
tumor is largely unknown. However, recent studies in in vivo models indicate that the anti-osteolytic drugs,
bisphosphonates, can inhibit the
tumor local expansion and the formation of
metastases. We further investigated the association between the presence of active osteoclasts and the aggressiveness of OS. We evaluated the presence of osteoclasts and the
mRNA of different osteoclast-related genes in
tumor biopsies from 16 OS patients and in three OS cell lines and the serum levels of
bone resorption markers in the same series and in 28 other patients.
Tumor-associated osteoclasts were found in 63 and 75% of cases by histological and
mRNA analysis. Among different
serum markers, only MMP-9 was significantly higher in OS cases (p=0.0001), whereas
TRACP 5b was significantly higher in metastatic patients compared to nonmetastatic patients (p=0.0509). Serum
TRACP 5b was significantly correlated to serum NTX (p<0.0001) and
cathepsin K mRNA in
tumor tissues (p=0.0153). In 8 patients we also analyzed
TRACP 5b serum level at follow-up and we verified a significant decrease of
TRACP 5b after primary
tumor removal (p=0.0117). In conclusion,
tumor-infiltrating osteoclasts are frequently found in OS and increased serum
TRACP 5b levels and the presence of active osteoclast at primary sites were positively associated with
tumor aggressiveness.