Osteonectin ( SPARC [secreted protein acidic and rich in cysteine, BM-40, 43K protein)

This is a secreted glycoprotein which modifies cell-extracellular matrix interactions It induces expression of type 1 plasminogen activator inhibitor and various matrix metalloproteins which are implicated in the degradation of the basement membrane and extracellular matrix, processes essential to tumour invasion and metastasis. Because of its wider expression, osteonectin lacks the specificty for bone tumours shown by osteocalcin.

Immunohistochemical expression

It is expressed in normal tissues undergoing proliferation and remodelling, such as during embryogenesis, morphogenesis, wound healing and angiogenesis. It is expressed by endothelium.

Overexpression by tumour cells has been reported in various malignancies including breast carcinoma, melanoma, glioma, meningioma, osteosarcoma and MFH. In colorectal and hepatocellular carcinoma, osteonectin is expressed by tumour-associated stromal cells but not by tumour cells themselves. Overexpression correlates with tumour progression and metastasis and inversely with patient survival.

In renal cell carcinoma, overexpression by tumour cells is restricted to sarcomatoid tumours1. In clear cell carcinoma, the fibroblasts and endothelium expressed SPARC.

References

1Sakai, N., Baba, M., Nagasima, Y. et al. SPARC expression in primary human renal cell carcinoma: upregulation of SPARC in sarcomatoid renal carcinoma. Human Pathol 2001;32:1064-1070

This page last revised 28.12.2001.

©SMUHT/PW Bishop