Targeting macrophages for cancer therapy disrupts bone homeostasis and impairs bone marrow erythropoiesis in mice bearing Lewis lung carcinoma tumors

2018 ◽  
Vol 331 ◽  
pp. 168-177 ◽  
Author(s):  
Weiqiang Jing ◽  
Li Zhang ◽  
Fei Qin ◽  
XiuXiu Li ◽  
Xing Guo ◽  
...  
2017 ◽  
Vol 243 (1) ◽  
pp. 66-77 ◽  
Author(s):  
Yan-Ping Wu ◽  
Jie Deng ◽  
Shu-Hua Ouyang ◽  
Zhong-Fu Mao ◽  
Guo-En Wang ◽  
...  

Polypeptides extracted from animal immune organs have been proved to exert immunomodulatory activities in previous reports. However, relative experimental data regarding the influence of a polypeptide mixture extracted from healthy calf spleen (lienal polypeptide [LP]) on the immune function in tumor therapy are limited, and the components in LP remain unclear. In the present study, the immune regulatory effect of LP was investigated in normal mice and Lewis lung carcinoma (LLC)-bearing mice treated with cyclophosphamide (CTX). The components of LP were identified by liquid chromatography–electrospray ionization-coupled with tandem mass spectrometry (LC–MS/MS) analysis and bioinformatic analysis. In LLC-bearing mice, LP showed a synergic antitumor effect with CTX, whereas LP alone did not present direct antitumor activity. Further, LP was found to enhance immune organ indexes, splenocyte number, and T lymphocyte subsets in normal mice and LLC-bearing mice treated with CTX. The decline of white blood cell and platelet counts, splenocyte proliferation activity, and peritoneal macrophage phagocytic function caused by CTX were also significantly suppressed by LP treatment in LLC-bearing mice. Notably, LP treatment significantly decreased the expression of phagocytosis-related proteins including CD47/signal regulatory protein α/Src homology phosphatase-1 in the tumor tissue of LLC-bearing mice treated with CTX. LC-MS/MS-based peptidomics unraveled the main polypeptides in LP with a length from 8 to 25 amino acids. Bioinformatics analysis further confirmed the possibility of LP to regulate immunity, especially in phagocytosis-related pathway. Our above findings indicated that LP can relieve the immunosuppression induced by chemotherapy and is a beneficial supplement in cancer therapy. Impact statement The immunomodulatory activities of polypeptides extracted from animal immune organs have incurred people’s interests since a long time ago. In this study, we investigated the immune regulation effects of a polypeptide mixture extracted from health calf spleen (lienal polypeptide [LP]) in Lewis lung carcinoma-bearing mice treated with cyclophosphamide (CTX). Liquid chromatography–electrospray ionization-coupled with tandem mass spectrometry-based peptidomics and bioinformatics analysis unraveled the main polypeptides in LP and further confirmed that LP is mainly associated with immune regulating pathway, especially in tumor cell phagocytosis-related pathway. Our study for the first time revealed that polypeptides from spleen can relieve the immunosuppression induced by CTX and is a beneficial supplement in cancer therapy.


Neoplasia ◽  
2005 ◽  
Vol 7 (3) ◽  
pp. 234-240 ◽  
Author(s):  
Vivek R. Shinde Patil ◽  
Erik B. Friedrich ◽  
Allison E. Wolley ◽  
Robert E. Gerszten ◽  
Jennifer R. Allport ◽  
...  

1998 ◽  
Vol 46 (5) ◽  
pp. 253-260 ◽  
Author(s):  
Mark A. Wright ◽  
Kristina Wiers ◽  
Kishore Vellody ◽  
Dragana Djordjevic ◽  
M. Rita I. Young

2018 ◽  
Vol 40 (1) ◽  
pp. 33-41 ◽  
Author(s):  
V V Sarnatskaya ◽  
L A Sakhno ◽  
L M Paziuk ◽  
L A Yushko ◽  
N K Rodionova ◽  
...  

Aim: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). Materials and Methods: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. Results: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. Conclusion: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes.


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