SPARC/osteonectin is involved in metastatic process to the lung during melanoma progression

Abstract

The existence of a "metastasis gene signature" that predisposes primary breast cancer cells to metastasize to the lungs has been recently highlighted by gene expression profiling studies. The combination of genes responsible for this process includes genes encoding several metalloproteinases as well as the gene encoding SPARC (secreted protein acidic and rich in cysteine)/osteonectin. SPARC is involved in normal tissue remodeling as it regulates the deposition of extracellular matrix, but also plays a role in neoplastic transformation. Aberrant SPARC expression has been detected both in stromal cells associated with cancer and in cancer cells. The main aim of this study was to investigate whether or not SPARC might be involved in directing metastasis of other types of cancer to the lung. We constructed a tissue microarray containing lung metastases from a variety of primary tumors in different organs and used immunohistochemistry to assess SPARC expression. We found SPARC overexpressed mainly in lung metastases from melanoma. We then assessed the expression of SPARC mRNA and protein in metastatic melanoma from different anatomic sites and in their corresponding primary tumors, and found that it is overexpressed in lung metastases. Our data strongly support the hypothesis that SPARC is involved in directing melanoma metastases specifically to the lung, which underpins its potential as prognostic marker and novel target for specific therapy.

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

“…Clinically, our findings are underlined by the high expression of SPARC that we observed in pulmonary metastases of melanoma biopsies. Interestingly, a recent study found SPARC overexpressed mainly in lung metastases from melanoma as compared with other primary tumours 46 .…”

Establishment of monoclonal HCC cell lines with organ site-specific tropisms

“…All these results suggest that IGTA1, VCAM1, SPARAC and ANGPTL4 could be the drivers of HCC metastatic tropisms. Although, the gains-of-functions or/and loss-of-functions of these candidates need be further explored [ 29 , 30 ].…”

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

“…Nonetheless, we note there are certain cases where MCP expression has been shown to oppose cancer development (51,52). SPARC protein is highly expressed in cancer cells and the stroma of certain cancers, including glioma, breast and cervical melanoma (53)(54)(55)(56), where it exhibits oncogenic roles in cell growth, invasion and apoptosis. Interestingly, SPARC has also been associated with tumor suppression by influencing these same processes (57).…”