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Bone is a major target for metastases in the most frequent solid tumors, which result in severe complications and are a major cause of pain. A bone metastasis gene expression signature was identified using human breast cancer cells in a mouse model. The bone metastasis-related genes encode secretory and cell surface proteins implicated in bone-homing (
CXCR4
), angiogenesis (
CTGF
and
FGF5
), invasion (
MMP
-
1
and
ADAMTS1
), and osteoclast recruitment (
IL11
). This signature superimposes on the 70-gene poor prognosis gene expression signature for breast cancer, and only
ADAMTS1
,
CTGF
and
IL11
were found to be overexpressed in human primary breast cancers with bone relapse. We analyzed the expression of the six bone metastasis-related genes in bone metastases from patients with different types of solid tumors, to assess its relevance in human clinical samples.
MMP
-
1
,
CXCR4
,
FGF5
and
CTGF
were found to be overexpressed in tumor cells of human bone metastases when compared to a human normal epithelial cell line. All the analyzed genes were overexpressed in the tumor cells of breast cancer bone metastases when compared to normal breast tissue. We did not detect any differences between the expression of these genes in bone metastases from breast cancer or from other types of solid tumors. Importantly, there was a significant correlation between the expressions of
IL11
/
CTGF
,
IL11
/
ADAMTS1
,
CTGF
/
CXCR4
,
CTGF
/
ADAMTS1
, and
MMP
-
1
/
ADAMTS1
, supporting the cooperative function of these proteins in the bone microenvironment, and the potential functional role of these genes in the establishment of bone metastases in vivo.