Taupin D, Ooi K, Yeomans N, Giraud A
Department of Medicine, University of Melbourne at Western Hospital, Australia.
Lab Invest. 1996 Jul;75(1):25-32.
Human intestinal trefoil factor (ITF), a mucosa-associated trefoil peptide, has been implicated in maintenance of mucosal integrity and may denote commitment to goblet cell differentiation. We have quantitated and localized ITF expression in normal and neoplastic colons, determined the molecular forms present, and examined the relationships among ITF expression and mucin production and increasing dysplasia. Normal and neoplastic human colonic mucosa (n = 30) were extracted for quantitation by ITF radioimmunoassay and size determination by gel filtration and immunoblotting. Paraffin sections of normal bowel, hyperplastic polyps, adenomatous polyps, and adenocarcinoma were examined for ITF immunohistochemistry and mucin histochemistry. The predominant molecular species in both normal and neoplastic colon was a 7-kd monomer. Staining was localized to goblet and Paneth cells and the luminal surface in normal colon and in most adenomatous polyps but not hyperplastic polyps; this colocalized with periodic acid-Schiff histochemistry. ITF staining of undifferentiated cells was seen with increasing dysplasia, and Golgi region immunoreactivity was highly conserved in adenocarcinoma, independent of the presence of periodic acid-Schiff-positive mucin. ITF concentration in colonic extracts was 10 to 200 pmol/g. Levels in normal (88.1 +/- 15.1 pmol/g) and malignant (90.1 +/- 12.7 pmol/g) tissue were comparable. In carcinomas, there were significant associations among ITF expression and degree of differentiation and mucin presence. Loss of expression was associated with tumor necrosis and advanced Duke's stage. ITF is uniformly processed in normal and neoplastic colons. Goblet cell-derived ITF is associated with stainable mucin production. ITF synthesis by non-goblet colonocytes, however, is highly conserved in neoplastic differentiation.
人肠三叶因子（ITF）是一种与黏膜相关的三叶肽，与维持黏膜完整性有关，可能意味着向杯状细胞分化的趋势。我们对正常结肠和肿瘤性结肠中ITF的表达进行了定量和定位，确定了其存在的分子形式，并研究了ITF表达与黏蛋白产生及发育异常加重之间的关系。提取正常和肿瘤性人类结肠黏膜（n = 30），通过ITF放射免疫测定法进行定量，并通过凝胶过滤和免疫印迹法确定大小。对正常肠、增生性息肉、腺瘤性息肉和腺癌的石蜡切片进行ITF免疫组织化学和黏蛋白组织化学检查。正常结肠和肿瘤性结肠中的主要分子形式均为7-kD单体。在正常结肠和大多数腺瘤性息肉而非增生性息肉中，染色定位于杯状细胞、潘氏细胞和管腔表面；这与过碘酸希夫组织化学共定位。随着发育异常加重，未分化细胞可见ITF染色，并且在腺癌中高尔基区免疫反应性高度保守，与过碘酸希夫阳性黏蛋白的存在无关。结肠提取物中ITF浓度为10至200 pmol/g。正常组织（88.1±15.1 pmol/g）和恶性组织（90.1±12.7 pmol/g）中的水平相当。在癌组织中，ITF表达与分化程度和黏蛋白存在之间存在显著关联。表达缺失与肿瘤坏死和杜克分期进展相关。ITF在正常结肠和肿瘤性结肠中均被一致加工。杯状细胞衍生的ITF与可染色黏蛋白产生相关。然而，非杯状结肠上皮细胞合成的ITF在肿瘤分化中高度保守。
