<br>细胞表面 GRP78：新兴的成像标记物和癌症治疗靶点,Journal of Controlled Release

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细胞表面 GRP78：新兴的成像标记物和癌症治疗靶点
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-10-29 , DOI: 10.1016/j.jconrel.2020.10.055
Masoud Farshbaf ₁ , Ahmad Yari Khosroushahi ₁ , Solmaz Mojarad-Jabali ₂ , Amir Zarebkohan ₃ , Hadi Valizadeh ₄ , Paul R Walker ₅

Affiliation

作为最致命的疾病之一，癌症经常对现有的治疗方法产生抵抗，因为它们并不针对进展性肿瘤内的所有细胞，例如肿瘤干细胞和增殖细胞。这常常导致侵袭性和转移性耐药肿瘤细胞亚群的富集、癌症复发并最终导致患者死亡。因此，迫切需要鉴定特异性标记物，通过这些标记物，靶向成像和/或治疗性“导弹”样药剂可以特异性地检测和/或根除异质肿瘤内的所有癌细胞，同时保持正常细胞完整。作为热休克蛋白 70 (HSP70) 超家族的一员，葡萄糖调节蛋白 78 (GRP78) 已被证明是内质网 (ER) 中的分子伴侣，主要响应正常细胞中的 ER 应激。 GRP78 在癌细胞和血管生成内皮细胞的表面过度表达，这使其成为不同类型的肽和抗体的有希望的靶标，可用于靶向癌症治疗或成像。在这篇综述中，我们讨论了肿瘤细胞中细胞表面 GRP78 (csGRP78) 的生物学过程、功能重要性和易位机制。作为癌症生物标志物，我们还回顾了 csGRP78 靶向治疗和成像的潜在应用，最后我们建议在 csGRP78 靶向之前制定一个简短的路线图，以实现靶向治疗诊断的意义。

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Cell surface GRP78: An emerging imaging marker and therapeutic target for cancer

As one of the deadliest diseases, cancer frequently resists existing therapeutics because they do not target all cells within a progressing tumor, for example both tumor stem and proliferating cells. This frequently results in enrichment of invasive and metastatic drug-resistant tumor cells subpopulations, cancer recurrence and eventually, patient mortality. Thus, there is an urgent need to identify specific markers, by which the targeted imaging and/or therapeutic “guided missile”-like agents can specifically detect and/or eradicate all cancer cells within a heterogeneous tumor, while leaving the normal cells intact. As a member of heat shock protein 70 (HSP70) superfamily, glucose regulated protein 78 (GRP78) has been documented as a molecular chaperone in the endoplasmic reticulum (ER) which mainly responds to ER stresses in normal cells. There is over-expression of GRP78 on the surface of cancer cells and angiogenic endothelial cells, which makes it a promising target for different types of peptides and antibodies that can be employed for targeted cancer therapy or imaging. In this review, we discuss the biological processes, functional importance and translocation mechanisms of cell surface GRP78 (csGRP78) in tumor cells. As a cancer biomarker, we also review the potential applications of csGRP78 targeted therapy and imaging and finally we suggest a brief roadmap ahead of csGRP78 targeting for targeted theranostic implications.

更新日期：2020-10-29

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