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原发性乳腺癌中Tn抗原表位(N-乙酰-D-半乳糖胺α-O-丝氨酸/苏氨酸)密度:侵袭性的功能预测指标

Tn epitope (N-acetyl-D-galactosamine alpha-O-serine/threonine) density in primary breast carcinoma: a functional predictor of aggressiveness.

作者信息

Springer G F

机构信息

Immunochemistry Research Department, Evanston Hospital, Department of Surgery, Northwestern University, Evanston, IL 60201.

出版信息

Mol Immunol. 1989 Jan;26(1):1-5. doi: 10.1016/0161-5890(89)90013-8.

DOI:10.1016/0161-5890(89)90013-8
PMID:2467192
Abstract

This interpretive review attempts to dovetail advanced work by different groups of investigators on blood group and carcinoma (CA) glycoconjugates that have terminal, immunoreactive Tn epitopes (GalNAc alpha-O-Ser/Thr), and on the interaction of those structures with complementary antibodies and lectins. Fenlon et al. (1987) and Leathem and Brooks (1987) found a positive correlation between primary breast CA aggressiveness and its affinity for Helix pomatia (HPA) lectin. This phenomenon was used successfully to accurately predict, in studies on 305 breast CA patients, early or late CA recurrence and patient survival time. The innate specificity of the large HPA combining groove (aside from its avid reactivity with appropriately spaced GalNAc alpha-O-) remains obscure, despite careful investigation for more than a decade (Baker et al., 1983). Leathem and Brooks presumed that HPA recognizes a hitherto "undefined biological marker" that indicates a breast CA's aggressiveness. Our own work has shown that the chemically fully defined Tn epitope, as measured with human polyclonal and murine monoclonal anti-Tn antibodies, occurs in immunoreactive form in approximately 90% of all breast and lung adenoCAs studied. Tn is occluded and non-reactive in healthy and non-CA-diseased tissues. We found that CA-associated Tn is an adhesion molecule in attachment to healthy cells; an increase in its density on breast CA cell membranes parallels greater aggressiveness of breast tumors in both humans and mice (the only species studied). Thus, Tn may be all or a major part of the postulated "as yet undefined biological marker" associated with high breast CA aggressiveness. Besides being helpful in the elucidation of some aspects of breast CA pathogenesis, these findings on primary breast CA have clinical implications in that they should facilitate stratification of breast CA patients for adjuvant treatment.

摘要

本解释性综述旨在将不同研究团队关于血型和癌(CA)糖缀合物(具有末端免疫反应性Tn表位(GalNAcα - O - Ser/Thr))以及这些结构与互补抗体和凝集素相互作用的前沿工作结合起来。Fenlon等人(1987年)以及Leathem和Brooks(1987年)发现原发性乳腺癌的侵袭性与其对苹果蜗牛(HPA)凝集素的亲和力之间存在正相关。在对305例乳腺癌患者的研究中,这一现象被成功用于准确预测早期或晚期癌症复发以及患者的生存时间。尽管经过十多年的仔细研究(Baker等人,1983年),但大的HPA结合槽的固有特异性(除了其与适当间隔的GalNAcα - O - 的强烈反应性之外)仍然不清楚。Leathem和Brooks推测HPA识别一种迄今“未定义的生物标志物”,该标志物表明乳腺癌的侵袭性。我们自己的研究表明,用人多克隆和鼠单克隆抗Tn抗体测量的化学上完全确定的Tn表位,以免疫反应形式出现在所研究的所有乳腺癌和肺腺癌的约90%中。Tn在健康和非癌症疾病组织中被封闭且无反应性。我们发现与癌症相关的Tn是一种附着于健康细胞的粘附分子;其在乳腺癌细胞膜上密度的增加与人类和小鼠(仅研究的物种)乳腺肿瘤的更大侵袭性平行。因此,Tn可能是与高乳腺癌侵袭性相关的假定“尚未定义的生物标志物”的全部或主要部分。除了有助于阐明乳腺癌发病机制的某些方面外,这些关于原发性乳腺癌的发现具有临床意义,因为它们应有助于对乳腺癌患者进行辅助治疗分层。

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