No abstract

No abstract

cDNA clones coding for tenascin, an extracellular matrix glycoprotein with a restricted tissue distribution, were isolated from a chicken fibroblast cDNA expression library using a specific tenascin antiserum. Antibodies eluted from the cDNA‐encoded fusion proteins reacted exclusively with tenascin. Limited trypsin treatment of purified tenascin resulted in a peptide which confirmed the deduced protein sequences. The largest clone encoding 632 amino acids showed a cysteine‐rich region containing 13 consecutive epidermal growth factor‐like repeats of unusual uniformity. Northern blot analysis revealed 8‐ to 9‐kb messages. Tenascin is shown to be induced in vitro by fetal calf serum as well as by transforming growth factor beta (TGF‐beta). A 4‐fold increase in tenascin secretion by chick embryo fibroblasts was seen after TGF‐beta treatment. The induction of tenascin protein synthesis was preceded by an increase of tenascin mRNA as determined by Northern blot analysis. The induction of tenascin was compared with fibronectin. The accumulation of the two extracellular matrix proteins in the medium was differentially affected by fetal calf serum and TGF‐beta and the increase was in both cases higher for tenascin.

Tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. The distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. Tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. An inhibition ELISA, testing homogenates of rat tumors, confirmed that tenascin was present in malignant but not in benign tumors. Thus, tenascin was consistently found to be a stromal marker for epithelial malignancy in the mammary gland. It is concluded that tenascin may be involved in the interactions between the epithelial and mesenchyme-derived (stromal) components of the mammary gland, which are known to influence epithelial carcinogenesis in this organ.Epithelial-mesenchymal interactions are important for the normal embryonic and postnatal development of many organs including the mammary gland (1). In addition, interactions between the epithelial and mesenchyme-derived (stromal) components are known to influence epithelial carcinogenesis in the mammary gland (2). Grobstein's studies suggested that induction of epithelial development is mediated by the extracellular matrix laid down by the organspecific mesenchyme (3). Thus, mesenchymal extracellular matrix molecules that show variations in their tissue distributions during development and neoplasia are potential mediators of mesenchymal-epithelial interactions. The extracellular matrix glycoprotein tenascin, which was previously described as myotendinous antigen (4), and may be identical to J1 (5), cytotactin (6), and glioma-associated extracellular matrix antigen (7), appears to be such a molecule. Tenascin is present in the early fetal rat mammary gland only in the dense mesenchyme closely surrounding the epithelial rudiment (8). It is not detectable in the mature rat mammary gland but is present in the stroma of rat mammary adenocarcinomas induced by the carcinogen N-methyl-Nnitrosourea (MNU; ref. 8). In the present study, the distribution of tenascin was examined in a wide variety of mammary tumors from laboratory animals to determine whether the presence of tenascin could be correlated with any particular type of neoplastic change in the mammary gland. Because of the potential clinical importance of an antigen that is not present in the normal gland but appears in mammary tumors, various human mammary lesions were also investigated. MATERIALS AND METHODSPreparation of Antiserum. Antiserum was raised in rabbits to tenascin purified from conditioned medium of chicken embryo fibroblast cultures, as described (8). The antiserum was found to cross-react with rat, mouse, and human tenascin.Tissues and Immunohistochemistry. Outbred Sprague-Dawley rats were treated with MNU for the induction of mammary tumors as described (8). Spontaneous mammary tumors were obtained from 7 of 213 untreated rats. Rat tumors and some tumor...

No abstract