Stromal expression of tenascin is inversely correlated to epithelial differentiation of hormone dependent tissues.
We were previously investigating the expression of the extracellular matrix glycoprotein tenascin in normal and malignant endometrial tissues of humans and rodents. These studies suggested that the expression of tenascin was induced by proliferating epithelia (normal and particularly malignant) and was downregulated with their differentiation. The aim of this study was to investigate the hormone dependency of tenascin expression in (a) the transplantable EnDA endometrial tumor model with or without estrogen deprivation (ovariectomy) of the animals, (b) DMBA-induced rat mammary tumors with or without a hormonal treatment of the animals [ovariectomy, antiestrogen (tamoxifen) or antiprogestin (ZK 98299) treatment] and (c) in the rat prostate of untreated or androgen deprived animals (orchiectomy, flutamide-, casodex- or cyproterone acetate (CPA)-treatment). 1. Estrogen withdrawal by ovariectomy did not affect tenascin expression in transplantable EnDA endometrial adenocarcinoma, meaning the entire extracellular space of the stromal mesenchyme was decorated by tenascin immunoreactivity. 2. In untreated DMBA-induced rat mammary tumors almost the entire extracellular space of the stroma was stained by tenascin immunoreactivity. Ovariectomy and antiestrogen treatment did not affect tenascin expression. In contrast, antiprogestin treatment induced terminal differentiation of mammary tumor cells and in parallel downregulated tenascin expression. 3. In the normal rat prostate no tenascin was detectable by immunocytochemistry. However, following androgen deprivation we found tenascin expression in the stroma of the prostate. The most prominent expression was observable after CPA-treatment, possibly due to its progestagenic potency. In conclusion, the hormones and antihormones tested show no direct effect on the stromal expression of tenascin. However, proliferative activity and a low degree of differentiation of the epithelium induces tenascin expression, whereas epithelial differentiation apparently shuts down tenascin expression. Preliminary in vitro studies suggest that paracrine acting growth factors trigger the hormonal regulation of tenascin expression.
Vollmer
G
G
Institut für Biochemische Endokrinologie, Medizinische Universität zu Lübeck, Germany.
Michna
H
H
Schneider
M R
MR
Knuppen
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000378:metabolism; D000728:Androgens / Q000502:physiology; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D016889:Endometrial Neoplasms / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006728:Hormones / Q000502:physiology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000378:metabolism*; D019063:Tenascin
D000728:Androgens; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D006728:Hormones; D019063:Tenascin; D015127:9,10-Dimethyl-1,2-benzanthracene