Abstract
BackgroundTenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors.MethodsWe analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues.ResultsFrom all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples.ConclusionsThe present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.
Highlights
Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues
The melanoma tissue microarrays (TMA) was constructed from frozen tissue samples of 34 malignant melanomas (5 primary tumors, 8 metastases from different organs and 21 lymph node metastases) and 6 control healthy cutaneous tissue samples
TNW score of 1.74 ± 0.15 (TNC) was detectable in all organs tested, except for normal breast and heart tissues
Summary
Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Tumor progression is influenced and controlled by activation of nearby stromal cells, including fibroblasts, endothelial cells and macrophages In their activated states, these cells modulate and reorganize the extracellular matrix and create a congenial microenvironment for the tumor cells. Tenascin-C (TNC) and tenascin-W (TNW) are two members of the tenascin family of large extracellular matrix glycoproteins (see [5] for information on the structure of tenascins). Their functions are associated with cellular mechanisms such as adhesion modulation, motility, proliferation and differentiation [5]. Its cancer-specific expression has been exploited to make TNC a promising target for different anti-cancer therapies, including the delivery of cytokines or radionuclides to the tumor using TNC-specific monoclonal antibodies [12,13,14] or aptamers [15,16]
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