A complex pattern of chemokine receptor expression is seen in osteosarcoma

Background: Osteosarcoma is the most frequent bone tumor in
childhood and adolescence. Patients with primary metastatic disease
have a poor prognosis. It is therefore important to better
characterize the biology of this tumor to define new prognostic
markers or therapeutic targets for tailored therapy. Chemokines and
their receptors have been shown to be involved in the development
and progression of malignant tumors. They are thought to be active
participants in the biology of osteosarcoma. The function of
specific chemokines and their receptors is strongly associated with
the biological context and microenvironment of their expression. In
this report we characterized the expression of a series of
chemokine receptors in the complex environment that defines
osteosarcoma. Methods: The overall level of chemokine receptor mRNA
expression was determined using TaqMan RT-PCR of microdissected
archival patient biopsy samples. Expression was then verified at
the protein level by immunohistochemistry using a series of
receptor specific antibody reagents to elucidate the cellular
association of expression. Results: Expression at the RNA level was
found for most of the tested receptors. CCR1 expression was found
on infiltrating mononuclear and polynuclear giant cells in the
tumor. Cells associated with the lining of intratumoral vessels
were shown to express CCR4. Infiltrating mononuclear cells and
tumor cells both showed expression of the receptor CCR5, while CCR7
was predominantly expressed by the mononuclear infiltrate. CCR10
was only very rarely detected in few scattered infiltrating cells.
Conclusion: Our data elucidate for the first time the cellular
context of chemokine receptor expression in osteosarcoma. This is
an important issue for better understanding potential
chemokine/chemokine receptor function in the complex biologic
processes that underlie the development and progression of
osteosarcoma. Our data support the suggested involvement of
chemokines and their receptors in diverse aspects of the biology of
osteosarcoma, but also contradict aspects of previous reports
describing the expression of these receptors in this tumor.