Dynamic changes of urine proteome in a Walker 256 tumor-bearing rat model

AbstractDespite advances in cancer treatments, early detection of cancer is still the most promising way to improve outcomes. Without homeostatic control, urine reflects early changes in the body and can potentially be used for early cancer diagnosis. In this study, a Walker 256 tumor rat model was established by subcutaneous injection of Walker 256 tumor cells. To identify urinary proteome changes during cancer development, urine samples from Walker 256 tumor-bearing rats were collected at five time points corresponding to before cancer cell implantation, before tumor mass palpability, at tumor mass appearance, during rapid tumor growth, and at cachexia. The urinary protein patterns changed significantly as the tumors progressed, as measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The urinary proteome of tumor-bearing rats was identified using Fusion Lumos mass spectrometry with label-free quantification. Then, 30 dynamically changed urinary proteins during cancer progression were selected as more reliable cancer biomarkers, and they were validated by targeted proteomics. Combined with the results of label-free and targeted proteome quantification, a total of 10 urinary proteins (HPT, APOA4, CO4, B2MG, A1AG, CATC, VCAM1, CALB1, CSPG4, and VTDB) changed significantly even before a tumor mass was palpable, and these early changes in urine could also be identified with differential abundance at late stages of cancer. Our study indicated that urine is a sensitive biomarker source for early detection of cancer.

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Insulin secretion in Walker 256 tumor cachexia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1990.258.6.e1033 ◽

1990 ◽

Vol 258 (6) ◽

pp. E1033-E1036 ◽

Cited By ~ 14

Author(s):

L. C. Fernandes ◽

U. F. Machado ◽

C. R. Nogueira ◽

A. R. Carpinelli ◽

R. Curi

Keyword(s):

Insulin Secretion ◽

Islets Of Langerhans ◽

Adult Male ◽

Male Rats ◽

Control Group ◽

Tumor Bearing ◽

Isolated Islets Of Langerhans ◽

Outflow Rate ◽

Walker 256 ◽

Walker 256 Tumor

The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats.

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Nocturnal depletion of hypothalamic dynorphin in anorexic walker-256 tumor-bearing rats

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(88)90017-2 ◽

1988 ◽

Vol 29 (3) ◽

pp. 541-545 ◽

Cited By ~ 4

Author(s):

T.D. Steele ◽

H.U. Bryant ◽

P.V. Malven ◽

G.K.W. Yim

Keyword(s):

Tumor Bearing ◽

Walker 256 ◽

Walker 256 Tumor

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Early urine proteome changes in the Walker-256 tail-vein injection rat model

Scientific Reports ◽

10.1038/s41598-019-50301-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Jing Wei ◽

Na Ni ◽

Wenshu Meng ◽

Youhe Gao

Keyword(s):

B Cell ◽

Rat Model ◽

Lung Tumor ◽

Whole Body ◽

Positive Regulation ◽

Urine Proteome ◽

Tail Vein ◽

Tail Vein Injection ◽

Differential Proteins ◽

Walker 256

Abstract Detection of cancer at its early stage is important for treatment. Urine, which is not regulated by homeostatic mechanisms, reflects early systemic changes throughout the whole body and can be used for the early detection of cancer. In this study, the Walker-256 tail-vein injection rat model was established to find whether the urine proteome could reflect early changes if tumor grown in lung. Urine samples from the control group (n = 7) and Walker-256 tail-vein injection group (n = 7) on days 2, 4, 6 and 9 were analyzed by label-free proteomic quantitative methods. On day 2, when lung tumor nodules did not appear, 62 differential proteins were identified. They were associated with epithelial cell differentiation, regulation of immune system processes and the classical complement activation pathway. On day 4, when lung tumor nodules appeared, 72 differential proteins were identified. They were associated with the innate immune response and positive regulation of phagocytosis. On day 6, when body weight began to decrease, 117 differential proteins were identified. On day 9, the identified 125 differential proteins were associated with the B cell receptor signaling pathway and the positive regulation of B cell activation. Our results indicate that (1) the urine proteome changed even on the second day after tail-vein injection of Walker-256 cells and that (2) compared to previous studies, the urine proteomes were different when the same cancer cells were grown in different organs.

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l-Glutamine supplementation promotes an improved energetic balance in Walker-256 tumor–bearing rats

Tumor Biology ◽

10.1177/1010428317695960 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769596 ◽

Cited By ~ 6

Author(s):

Heber Amilcar Martins ◽

Roberto Barbosa Bazotte ◽

Geraldo Emilio Vicentini ◽

Mariana Machado Lima ◽

Flavia Alessandra Guarnier ◽

...

Keyword(s):

Phosphoenolpyruvate Carboxykinase ◽

Experimental Period ◽

Plasma Corticosterone ◽

Glutamine Supplementation ◽

Tumor Bearing ◽

Male Wistar Rats ◽

Energetic Balance ◽

Walker 256 ◽

Immunohistochemical Techniques ◽

Walker 256 Tumor

We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor–bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed. Protein expression levels of key enzymes of gluconeogenesis, that is, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, were analyzed by western blot and immunohistochemical techniques. In addition, plasma corticosterone, glucose, insulin, and urea levels were evaluated. The WTG group showed significantly increased plasma glucose and insulin levels ( p < 0.05); however, plasma corticosterone and urea remained unchanged. Moreover, the WTG group showed increased immunoreactive staining for jejunal phosphoenolpyruvate carboxykinase and increased expression of duodenal glucose-6-phosphatase. Furthermore, the WTG group presented with less intense cancer cachexia and slower tumor growth. These results could be attributed, at least partly, to increased intestinal gluconeogenesis and insulinemia, and better glycemia maintenance during fasting in Walker-256 tumor rats on a diet supplemented with l-glutamine.

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