Clinical impact and functional aspects of tenascin‐C expression during glioma progression

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Abstract
The extracellular matrix protein tenascin‐C is expressed in processes like embryogenesis and wound healing and in neoplasia. Tenascin‐C expression in gliomas has been described previously; however, the relation to clinical data remains inconsistent. Generally, analysis of tenascin‐C function is difficult due to different alternatively spliced isoforms. Our studies focus on changes in tenascin‐C expression in human gliomas, correlating these changes with tumor progression and elucidating the functional role of the glioma cell‐specific tenascin‐C isoform pool. Eighty‐six glioma tissues of different World Health Organization (WHO) grades were analyzed immunohistochemically for tenascin‐C expression. The influence of the specific tenascin‐C isoforms produced by glioblastoma cells on proliferation and migration was examined in vitro using blocking antibodies recognizing all isoforms. In general, tenascin‐C expression increased with tumor malignancy. Perivascular staining of tenascin‐C around tumor‐supplying blood vessels was observed in all glioblastoma tissues, whereas in WHO II and III gliomas, perivascular tenascin‐C staining appeared less frequently. The appearance of perivascular tenascin‐C correlated significantly with a shorter disease‐free time. Analysis of proliferation and migration in the presence of blocking antibodies revealed an inhibition of proliferation by around 30% in all 3 glioblastoma cell cultures, as well as a decrease in migration of 30.6–46.7%. Thus we conclude that the endogenous pool of tenascin‐C isoforms in gliomas supports both tumor cell proliferation and tumor cell migration. In addition, our data on the perivascular staining of tenascin‐C in WHO II and III gliomas and its correlation with a shorter disease‐free time suggest that tenascin‐C may be a new and potent prognostic marker for an earlier tumor recurrence.