Tenascin is a stromal marker for epithelial malignancy in the mammary gland.

Abstract

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...

Expression and degeneration of tenascin-C in human lung cancers

“…In normal lungs, in contrast, weak staining was found in the bronchial basement membrane and vascular walls in line with earlier findings (Soini et al, 1993). Thus, TN-C positivity is not restricted to malignant neoplasms and is not specific for the cancer tissue, as initially proposed (Mackie et al, 1987). It rather appears to be present at interfaces between different types of cell dynamics.…”

“…Immunohistochemical studies have revealed that TN-C appears at specific times and locations in the embryo and also occasionally in normal adult tissues (for a review, see Sakakura, 1995). Subsequent to the initial proposal that it might be a stromal marker for epithelial cancers (Mackie et al, 1987), it has been shown to be expressed at greater levels in malignant than in benign tumours in many organs, with a tendency for increase in advanced stages (Bourdon et al, 1983;Anbazhagen et al, 1990; Van Eyken et al, 1990;Vollmer et al, 1990; Koukoulis et al, 1991;Sakakura et al, 1991;Borsi et al, 1992). A high-molecular-weight isoform that is generated by alternative splicing of RNAs of TN-C was found predominantly in breast (Borsi et al, 1992), prostatic (Ibrahim et al, 1993) and colorectal (Hauptmann et al, 1995) cancers.…”

Involvement of Large Tenascin-C Splice Variants in Breast Cancer Progression

“…Originally only reported as a stromal marker of epithelial malignancy in breast tissues, 43 it is now clear that Tn-C is also expressed around normal ducts and benign lesions of the breast. 44 -46 Since comparisons of Tn-C expression and outcome of patients yielded conflicting results, the distribution and site of synthesis in breast cancer have been considered to have greater prognostic significance than its presence or absence.…”

Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours

“…In general, TN can be found in areas associated with cellular proliferation and tissue reorganisation, for example, during wound healing in human skin (Latijnhouwers et al, 1994) and in breast tissue during gestation and lactation (Howeedy et al, 1990). TN expression also varies in normal breast tissue depending on the stage of the menstrual cycle (Ferguson et al, 1990) and is overexpressed in the stroma of breast cancer (Mackie et al, 1987) and other solid tumours (Zagag et al, 1995;Ibrahim et al, 1993;Yamada et al, 1992;Natali et al, 1991;Koukoulis et al, 1991;Vollmer et al, 1990). It has been proposed that production of TN is under paracrine control; several growth factors, including transforming growth factor beta (TGF-fl), have been implicated in regulation of TN expression (Pearson et al, 1988 In the section of normal ovary, the observed staining was limited to a fine line around the smooth muscle cells of blood vessels with negligible reaction in the surrounding ovarian stroma (Figure 2a).…”