Background
During recent years increasing evidence has emerged showing that the microenvironment plays a prominent role in determining tumor behavior.[1–4] 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. Accepting an active role of the microenvironment for tumor progression, it will be important to consider how the activated tumor stroma can be harnessed for clinical benefit. Extracellular matrix proteins specifically expressed in the tumor stroma could thus represent promising predictive/diagnostic biomarkers or target molecules for therapeutics.
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] Both proteins share highest expression during embryonic development and reduced and very restricted expression in adult tissues.[6] TNC, the best-described family member, reappears during pathological conditions such as cancer, inflammation or wound-healing.[7,8] Soon after its initial identification, TNC was proposed as a stromal marker in breast cancer.[9] Since then, many more studies shown that TNC expression could have predictive value for local tumor recurrence and metastatic dissemination in many aggressive cancers (for reviews see [2,10,11]. 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[12–14] or aptamers.[15,16]
Similar physiological expression patterns as well as shared functions of TNW with TNC prompted us to investigate the presence of the newest tenascin family member, TNW in different human cancers. TNW expression was detected in a large majority of human breast tumors, showing enrichment in low-grade compared to high-grade tumors.[17] In colorectal cancer, TNW expression was restricted to the tumor-associated microenvironment, while the protein was not detectable in the corresponding healthy tissue.[18] In brain tumors, all glioma subtypes tested (oligodendroglioma, astrocytoma and glioblastoma) were enriched in TNW in comparison to healthy control brain tissues.[19] Noticeably, in all glioblastoma samples analyzed the localization of TNW was perivascular.[19]
Encouraged by the highly tumor-specific expression of TNW in breast, colon, and brain tumors, we now extended our expression study to many more types of solid tumors. We show here, that TNW expression displays an even higher specificity for cancer-related microenvironments than TNC. Hence, TNW represents a novel attractive cancer biomarker of broad potential for tumor detection, prediction and targeting approaches.
BMC Clin Pathol. 2012;12(14) © 2012 BioMed Central, Ltd.
