Ryder S D, Parker N, Ecclestone D, Haqqani M T, Rhodes J M
Department of Medicine, University of Liverpool, England.
Gastroenterology. 1994 Jan;106(1):117-24. doi: 10.1016/s0016-5085(94)94775-9.
BACKGROUND/AIMS: The TF antigen (galactose-beta 1,3-N-acetylgalactosamine alpha) is overexpressed in malignant and premalignant colonic epithelium. Previous studies have shown that peanut lectin (PNA), which binds TF, is mitogenic for normal human colonic epithelium. This study aimed to determine its effect on abnormal colonic epithelium.
Crypt cell proliferation rate (CCPR) was measured using vincristine arrest and mucus synthesis by incorporation of radiolabeled N-acetyl glucosamine in colonoscopic biopsy specimens cultured with and without PNA.
Unstimulated CCPR was greater in patients with ulcerative colitis than in patients with histologically normal colon. PNA (25 micrograms/mL) produced a 25% average increase in CCPR in tissues from patients with ulcerative colitis, Crohn's disease, and colonic polyps. In ulcerative colitic biopsy specimens incubated with PNA, CCPR increased to more than double that of unstimulated normal colonic epithelium. In controls, the response to PNA was greater when adjacent specimens were positive for PNA (avidin-biotin) histochemistry than when they were negative. Mucus synthesis was increased by an average 75% over 24 hours by PNA.
Increased TF expression by premalignant epithelia may allow stimulation of proliferation by dietary galactose N-acetylgalactosamine-binding lectins. If the hyperplasia-dysplasia cancer hypothesis is correct, this could explain the increased colon cancer risk in ulcerative colitis.
背景/目的：TF抗原（半乳糖-β1,3-N-乙酰半乳糖胺α）在恶性和癌前结肠上皮中过度表达。先前的研究表明，与TF结合的花生凝集素（PNA）对正常人结肠上皮有促有丝分裂作用。本研究旨在确定其对异常结肠上皮的影响。
在添加和不添加PNA培养的结肠镜活检标本中，使用长春新碱阻滞法测量隐窝细胞增殖率（CCPR），并通过掺入放射性标记的N-乙酰葡糖胺来检测黏液合成。
溃疡性结肠炎患者未受刺激的CCPR高于组织学正常结肠的患者。PNA（25微克/毫升）使溃疡性结肠炎、克罗恩病和结肠息肉患者组织中的CCPR平均增加25%。在与PNA孵育的溃疡性结肠炎活检标本中，CCPR增加至未受刺激的正常结肠上皮的两倍以上。在对照组中，当相邻标本PNA（抗生物素蛋白-生物素）组织化学呈阳性时，对PNA的反应大于阴性时。PNA使黏液合成在24小时内平均增加75%。
癌前上皮中TF表达增加可能使膳食中半乳糖N-乙酰半乳糖胺结合凝集素刺激增殖。如果增生-发育异常-癌症假说是正确的，这可以解释溃疡性结肠炎患者结肠癌风险增加的原因。
