Abstract:
Over the past 20 years, increasing evidence has demonstrated that immunoglobulins (Igs) can be widely generated from non B cells, including normal and malignant mammary epithelial cells. In normal breast tissue, the expression of IgG and IgA has been identified in epithelial cells of mammary glands during pregnancy and lactation, which can be secreted into milk, and might participate in neonatal immunity. On the other hand, non B-IgG is highly expressed in breast cancer cells, correlating with the poor prognosis of patients with breast cancer. Importantly, a specific group of IgG, bearing a unique N-linked glycan on the Asn162 site and aberrant sialylation modification at the end of the novel glycan (referred to as sialylated IgG (SIA-IgG)), has been found in breast cancer stem/progenitor-like cells. SIA-IgG can significantly promote the capacity of migration, invasiveness, and metastasis, as well as enhance self-renewal and tumorigenicity in vitro and in vivo. These findings suggest that breast epithelial cells can produce Igs with different biological activities under physiological and pathological conditions. During lactation, these Igs could be the main source of milk Igs to protect newborns from pathogenic infections, while under pathological conditions, they display oncogenic activity and promote the occurrence and progression of breast cancer.
摘要:
在过去的20年里,越来越多的证据表明,免疫球蛋白(Ig)可以从非B细胞广泛产生,包括正常和恶性乳腺上皮细胞。在正常乳腺组织中,在妊娠和哺乳期乳腺上皮细胞中已发现IgG和IgA的表达,可以分泌到牛奶中,并可能参与新生儿免疫。另一方面,非B-IgG在乳腺癌细胞中高表达,与乳腺癌患者预后不良有关。重要的是,一组特定的IgG,在Asn162位点上具有独特的N-连接的聚糖,并且在新型聚糖(称为唾液酸化IgG(SIA-IgG))的末端具有异常的唾液酸化修饰,已在乳腺癌干/祖细胞中发现。SIA-IgG能显著促进迁移能力,侵入性,和转移,以及在体外和体内增强自我更新和致瘤性。这些发现表明,乳腺上皮细胞在生理和病理条件下可以产生具有不同生物学活性的Ig。哺乳期,这些Igs可能是牛奶Igs的主要来源,以保护新生儿免受病原体感染,在病理条件下,它们显示致癌活性,促进乳腺癌的发生和进展。