Mannello Ferdinando, Tonti Gaetana A M
Department of Biomolecular Sciences, Section of Clinical Biochemistry, University Carlo Bo, Urbino, Italy.
Oncologist. 2008 Jul;13(7):761-8. doi: 10.1634/theoncologist.2008-0110. Epub 2008 Jul 2.
The expression of erythropoietin (Epo) and the Epo receptor (EpoR) has been detected in healthy tissue as well as in a variety of human cancers, including breast. Functional Epo/EpoR signaling in cancer cells, which contributes to disease initiation/progression, is not completely straightforward and is difficult to reconcile with the clinical practice of preventing/treating anemia in cancer patients with recombinant Epo. Preclinical and clinical investigations have provided contrasting results, ranging from a beneficial role that improves the patient's overall survival to a negative impact that promotes tumor growth progression. A careful gathering of Epo/EpoR biomolecular information enabled us to assemble an unexpected jigsaw puzzle which, via distinct JAK-dependent and JAK-independent mechanisms and different internalization/recycling as well as ubiquitination/degradation pathways, could explain most of the controversies of preclinical and clinical studies. However, until the mechanisms of the contrasting literature data are resolved, this new point of view may shed light on the Epo/EpoR paracrine/autocrine system and function, providing a basis for further studies in order to achieve the highest possible benefit for cancer patients.
在健康组织以及包括乳腺癌在内的多种人类癌症中，均已检测到促红细胞生成素（Epo）和促红细胞生成素受体（EpoR）的表达。癌细胞中功能性Epo/EpoR信号传导有助于疾病的起始/进展，但其情况并非完全简单明了，并且难以与使用重组Epo预防/治疗癌症患者贫血的临床实践相协调。临床前和临床研究得出了相互矛盾的结果，从改善患者总生存期的有益作用到促进肿瘤生长进展的负面影响不等。对Epo/EpoR生物分子信息的仔细收集使我们能够拼凑出一幅意想不到的拼图，通过不同的JAK依赖性和JAK非依赖性机制以及不同的内化/再循环以及泛素化/降解途径，可以解释临床前和临床研究中的大多数争议。然而，在解决相互矛盾的文献数据的机制之前，这种新观点可能会阐明Epo/EpoR旁分泌/自分泌系统及其功能，为进一步研究提供基础，以便为癌症患者带来最大可能的益处。
