scholarly journals The neutrophil protein CD177 is a novel PDPN receptor that regulates human cancer-associated fibroblast physiology

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260800
Author(s):  
Jillian L. Astarita ◽  
Shilpa Keerthivasan ◽  
Bushra Husain ◽  
Yasin Şenbabaoğlu ◽  
Erik Verschueren ◽  
...  

The cancer-associated fibroblast (CAF) marker podoplanin (PDPN) is generally correlated with poor clinical outcomes in cancer patients and thus represents a promising therapeutic target. Despite its biomedical relevance, basic aspects of PDPN biology such as its cellular functions and cell surface ligands remain poorly uncharacterized, thus challenging drug development. Here, we utilize a high throughput platform to elucidate the PDPN cell surface interactome, and uncover the neutrophil protein CD177 as a new binding partner. Quantitative proteomics analysis of the CAF phosphoproteome reveals a role for PDPN in cell signaling, growth and actomyosin contractility, among other processes. Moreover, cellular assays demonstrate that CD177 is a functional antagonist, recapitulating the phenotype observed in PDPN-deficient CAFs. In sum, starting from the unbiased elucidation of the PDPN co-receptome, our work provides insights into PDPN functions and reveals the PDPN/CD177 axis as a possible modulator of fibroblast physiology in the tumor microenvironment.

Author(s):  
Robert M. Glaeser ◽  
Thea B. Scott

The carbon-replica technique can be used to obtain information about cell-surface structure that cannot ordinarily be obtained by thin-section techniques. Mammalian erythrocytes have been studied by the replica technique and they appear to be characterized by a pebbly or “plaqued“ surface texture. The characteristic “particle” diameter is about 200 Å to 400 Å. We have now extended our observations on cell-surface structure to chicken and frog erythrocytes, which possess a broad range of cellular functions, and to normal rat lymphocytes and mouse ascites tumor cells, which are capable of cell division. In these experiments fresh cells were washed in Eagle's Minimum Essential Medium Salt Solution (for suspension cultures) and one volume of a 10% cell suspension was added to one volume of 2% OsO4 or 5% gluteraldehyde in 0.067 M phosphate buffer, pH 7.3. Carbon replicas were obtained by a technique similar to that employed by Glaeser et al. Figure 1 shows an electron micrograph of a carbon replica made from a chicken erythrocyte, and Figure 2 shows an enlarged portion of the same cell.


2019 ◽  
Author(s):  
Maha Al-Mozaini ◽  
Ibtihag S. Alsharif ◽  
Al-Hussain J. Alzahrani ◽  
Zakia Shinwari ◽  
Magid Halim ◽  
...  

Author(s):  
Maha Al-Mozaini ◽  
Ibtihag Alsharif ◽  
Alhusain Alzahrani ◽  
Zakia Shinwari ◽  
Magid Halim ◽  
...  

2009 ◽  
Vol 17 (3) ◽  
pp. 247-257 ◽  
Author(s):  
Richard T. Blankley ◽  
Nicola J. Robinson ◽  
John D. Aplin ◽  
Ian P. Crocker ◽  
Simon J. Gaskell ◽  
...  

2014 ◽  
Vol 103 (1) ◽  
pp. 140-146 ◽  
Author(s):  
Thijs C. van Holten ◽  
Onno B. Bleijerveld ◽  
Patrick Wijten ◽  
Philip G. de Groot ◽  
Albert J.R. Heck ◽  
...  

2021 ◽  
pp. 2100031
Author(s):  
Peng Zheng ◽  
Chenglinzi Liu ◽  
Yaoqin Wu ◽  
Ruifeng Xu ◽  
Ying Chen ◽  
...  

2016 ◽  
Vol 39 (5) ◽  
pp. 1761-1776 ◽  
Author(s):  
Lei Chen ◽  
Yang Lu ◽  
Jun Wen ◽  
Xu Wang ◽  
Lingling Wu ◽  
...  

Background/Aims: Individuals possessing a single kidney are at greater risk of renal injury upon exposure to harmful stimuli. This study aimed to explore the pathogenesis of renal injury in glomerulonephritis with versus without unilateral nephrectomy (UNX). Methods: Histological analysis and label-free quantitative proteomics were performed on two models—the Habu snake venom-induced glomerulonephritis model with versus without UNX (HabuU and Habu models, respectively). The role of villin 1, a differentially expressed protein (DEP) in mouse mesangial cells, was investigated. Results: Persistent mesangiolysis and focal hypercellularity together with reduced activation of cell proliferation in the HabuU model induced more serious renal injury compared with that in the Habu model. The DEPs between the two models were identified by label-free liquid chromatography-mass spectrometry. The KEGG pathway results indicated that regulation of actin cytoskeleton and focal adhesion were specifically enriched in the HabuU model. The cytoskeleton regulation protein villin 1 was downregulated in the HabuU model, but unchanged in the Habu model. Knockdown of villin 1 promoted apoptosis and inhibited the proliferation of mouse mesangial cells, suggesting villin 1 to be involved in qlomerular lesion self-repair insufficiency. Conclusion: By assessing the proteomic profiles of the two models, this study identified several important differences, particularly villin 1 expression, in regulatory mechanisms between the two models. Our findings provide novel insight into the mechanism of serious renal injury in glomerulonephritis with UNX.


2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Zheyu Zhang ◽  
Wenbo Wang ◽  
Ling Jin ◽  
Xin Cao ◽  
Gonghui Jian ◽  
...  

Yinchenwuling powder (YCL) is an effective traditional Chinese medicine formula to modulate lipid levels. In this study, we established hyperlipidemic rat models and treated them with YCL. The serum concentrations of lipid, malondialdehyde (MDA), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) were measured. Adventitia-free vascular proteins between hyperlipidemic rats and YCL-treated rats were identified using iTRAQ-based quantitative proteomics research approach. Proteins with 1.3-fold difference were analyzed through bioinformatics, and proteomic results were verified by Western blot. The results showed that the serum levels of TC, TG, LDL-C, ET-1, and MDA were significantly decreased, whereas the HDL-C and CGRP levels were significantly increased in the YCL-treated group. Proteomics technology identified 4,382 proteins, and 15 proteins were selected on the basis of their expression levels and bioinformatics. Of these proteins, 2 (Adipoq and Gsta1) were upregulated and 13 (C3, C4, C6, Cfh, Cfp, C8g, C8b, Lgals1, Fndc1, Fgb, Fgg, Kng1, and ApoH) were downregulated in the YCL-treated rats. Their functions were related to immunity, inflammation, coagulation and hemostasis, oxidation and antioxidation, and lipid metabolism and transport. The validated results of ApoH were consistent with the proteomics results. This study enhanced our understanding on the therapeutic effects and mechanism of YCL on hyperlipidemia.


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