Potential applications of tenascin C for cancer diagnosis and therapy

Abstract

Tenascins are a family of four multimeric extracellular matrix glycoproteins: tenascin C, X, R and W. The fi rst described member of the family was tenascin C. This protein is also known as glial mesenchymal extracellular matrix protein, myotendinous antigen, hexabrachion, cytotactin, J1220 200, neuronectin. Tenascin C is a hexamer; each arm of the hexabrachion comprises an amino-terminal assembly domain, epidermal growth factor-like repeats, fi bronectin type III domain and globular fi brinogen-homology domain.

The tenascin C pattern of expression is variable depending on the developmental stage of the organism, and its expression changes dramatically under many diff erent pathological conditions. During embriogenesis, tenascin C is especially prevalent in the developing central nervous system, in mesenchyme in sites of mesenchymal-epithelial interactions, and in developing connective tissues. In normal adult tissues, tenascin C expression is less abundant, but it is induced during wound healing, nerve regeneration, tissue involution and in pathological conditions including vascular diseases, tumourigenesis, and metastases. Expression of tenascin C in both development and disease is induced by various pro- and anti-infl ammatory cytokines, growth factors, but also by reactive oxygen species, hypoxia, and by mechanical stress.

The contribution of tenascin C to tumor development relies on two main actions: (1) its direct stimulation of the tumor cells by activation of their proliferation, invasion and migration capacities and (2) through its impact on endothelial cells by promotion of angiogenesis. Besides the role in primary tumor development, tenascin C participates in process of metastasis and in escape from tumor immunosurveillance.

Tenascin C has been reported as an indicator of bad prognosis, in tumors of breast, kidney, bladder, intrahepatic bile ducts, lung, larynx, hypopharynx and brain. On the other hand in cervical cancer a high expression of tenascin C was correlated with good prognosis. In addition, tenascin C expression represents a predictive value for local recurrence of brain tumors, and tenascin C fragments for lung cancer.

Tenascin C may be not only a diagnostic tool, and its application in tumors localization and treatment is also investigated. The new strategies are based on antibodies, antisense oligonucleotides, ribozymes, aptamers, and intervention with interference RNA.