Changes in the Urinary Proteome in a Patient-Derived Xenograft (PDX) Nude Mouse Model of Colorectal Tumor

Abstract

In this report, the urinary proteome from a patient-derived xenograft (PDX) model was examined at the peptide level to study the origins of urinary proteins in tumor-bearing nude mice. Urine was collected from PDX mice before and after colorectal tumor implantation. A total of 4,318 unique peptides were identified, and 78 unambiguous human-origin peptides were discerned in the PDX model urine. Unlike the differential urinary protein composition of tumor-bearing immunocompetent rat models, the differential urinary proteins in the PDX model did not include host immune-response proteins. This study demonstrates that tumor-secreted proteins can be observed in the urine proteome of the PDX model. However, immune-response proteins, which are very early candidate tumor biomarkers, are not present in the urine of PDX model mice; this absence is due to immune deficiency. Therefore, immunodeficient animals may not be suitable models for searching for early immunity-associated tumor biomarkers in the urine.

Rapid screening for individualized chemotherapy optimization of colorectal cancer: A novel conditional reprogramming technology-based functional diagnostic assay.

“…All animal experiments were performed under sterile conditions at Percans Oncology Inc. specific-pathogen free facility and carried out in accordance with the National Institutes of Health guide for the care and use of laboratory animals. The procedure of PDX model establishment was referred to previous reports [14 , 26] . Briefly, 6–8 week-old female NOD/SCID mice (Beijing HFK Bio-Technology Co., LTD, Beijing, China) were used for the studies.…”

“…In addition, the establishment of tumor cell lines is hindered by the low rate of success (1–10%, depending on the tissue of origin and state of disease progression). Patient-derived xenograft (PDX) [13] , [14] , [15] and tumor organoids [16] , [17] , [18] have been considered more clinically relevant models for original patient tumors. Yet the use of such systems still facing hurdles such as high cost, long duration and technical difficulties, etc.…”

Urinary protein analysis in mice lacking major urinary proteins

“…An ~25-kDa band was detected only in wild-type females, as shown in Fig. 2C , but proteins of this band seem unlikely to be MUPs because the 25 kDa band is not always detected (data not shown), as shown in the study of Liu et al [ 21 ]; moreover, bands have also been detected in some MUP-KO mice (data not shown). Although we did not identify the ~25-kDa proteins in the present study, lipocalin 2 [ 22 ] is one possible candidate.…”

Application Research of Individualized Conditional Reprogramming System to Guide Treatment of Gastric Cancer

“…Chemosensitivity in cell culture alone often cannot recreate microenvironments or tumor heterogeneity in tumor tissues, so the results are often not accurate. At present, the model of "human tumor tissue xenotransplantation (PDX)" is the most recognized in the world (5)(6)(7). In this model, a small piece of tumor tissue taken from the patient is implanted into an experimental mouse to simulate its original growth environment, thus preserving the characteristics of the patient and the tumor to the maximum extent.…”