Radiation Immuno-Oncology Group, Center for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, Technische Universität München (TUM), Einstein Str. 25, 81675, Munich, Germany.
Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, Winterthurer Str. 258c, CH-8057, Zurich, Switzerland.
Cell Stress Chaperones. 2019 Sep;24(5):969-978. doi: 10.1007/s12192-019-01024-9. Epub 2019 Aug 3.
The concentration of circulating heat shock protein 70 (Hsp70) was measured in liquid biopsies of canine tumor patients as a potential biomarker. Compared with rodent tumor models, spontaneously occurring tumors in pet dogs reflect the clinical situation of human patients better, as dogs cohabitate with their owners in the same environment, reach a much older age than rodents, can provide blood samples much more frequently, and receive up-to-date medical care and, similar to humans, their tumors show a high genetic heterogeneity. Due to the species-specific sequence homology of human and canine Hsp70, two human enzyme-linked immunosorbent assay (ELISA) systems (R&D and lipHsp70) were used to measure canine Hsp70 concentrations in serum and plasma. In general, higher Hsp70 concentrations were found in serum compared with plasma samples of dogs, and the lipHsp70 ELISA detected higher peak concentrations of Hsp70 in a broader range than the R&D ELISA. Compared with a tumor-free control group, serum Hsp70 concentrations were higher in tumor-bearing dogs, irrespective of breed, age, body weight, and gender. A sub-classification of the different tumors according to their cytological characteristics revealed significantly elevated Hsp70 serum concentrations in dogs with round cell tumors (p < 0.01), a heterogeneous group of malignancies with hematopoietic origin such as mast cells, plasma cells, lymphocytes, histiocytes, and melanomas. Future studies with larger patient cohorts and well-defined tumor sizes are necessary to elucidate the role of serum Hsp70 as a biomarker for tumor detection and monitoring of outcome in pet animals.
循环热休克蛋白 70（Hsp70）浓度在犬肿瘤患者的液体活检中作为一种潜在的生物标志物进行了测量。与啮齿动物肿瘤模型相比，宠物犬中自发发生的肿瘤能更好地反映人类患者的临床情况，因为狗与它们的主人生活在相同的环境中，寿命比啮齿动物长，能更频繁地提供血液样本，接受最新的医疗护理，并且与人类相似，它们的肿瘤具有高度的遗传异质性。由于人类和犬 Hsp70 的种特异性序列同源性，使用两种人类酶联免疫吸附测定（ELISA）系统（R&D 和 lipHsp70）来测量血清和血浆中的犬 Hsp70 浓度。一般来说，与犬血浆样本相比，血清中 Hsp70 的浓度更高，而 lipHsp70 ELISA 检测到的 Hsp70 峰值浓度在更宽的范围内比 R&D ELISA 更高。与无肿瘤对照组相比，患有肿瘤的犬的血清 Hsp70 浓度更高，与品种、年龄、体重和性别无关。根据细胞学特征对不同肿瘤进行分类，结果显示圆形细胞瘤犬的血清 Hsp70 浓度显著升高（p<0.01），圆形细胞瘤是一组具有造血来源的恶性肿瘤，如肥大细胞、浆细胞瘤、淋巴细胞、组织细胞和黑色素瘤。需要进行更大的患者队列和明确肿瘤大小的未来研究，以阐明血清 Hsp70 作为宠物动物肿瘤检测和监测结果的生物标志物的作用。
