scholarly journals Human Neutrophil Peptides 1-3 – Early Markers in Development of Colorectal Adenomas and Carcinomas

2008 ◽  
Vol 25 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Henning Mothes ◽  
Christian Melle ◽  
Günther Ernst ◽  
Roland Kaufmann ◽  
Ferdinand von Eggeling ◽  
...  
Keyword(s):  
Human Neutrophil ◽  
Tumour Growth ◽  
Tumour Response ◽  
Colorectal Adenomas ◽  
Cancer Stage ◽  
Tumour Stage ◽  
Laser Capture Microscopy ◽  
Early Markers ◽  
Laser Capture

Expression of Human Neutrophil Peptides (HNP) 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin-expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment.To further specify the role of α-defensins in tumourigenesis and progression, HNP1–3 were analyzed in colorectal adenomas and carcinomas of 87 patients and quantified in relation to cancer stage and grading. Using the ProteinChip arrays, HNP1–3 were found upregulated in both colorectal adenomas and carcinomas. By combining the array with Laser capture microscopy we were able to confirm that HNP1–3 are expressed by tumour cells but not by neutrophils or other tumour invading cells. These findings suggest that α-defensins are more likely to contribute to tumour growth than they are to mount an effective host anti-tumour response. However, the amount of HNP-expression was not found to be related to tumour stage, grading, and serological tumour markers.

scholarly journals Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Tumour Microenvironment ◽  
Tube Formation ◽  
Tissue Remodelling ◽  
Colon Cancers ◽  
Inflammatory Bowel ◽  
Ion Pumping ◽  
G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

scholarly journals Stimulus-response coupling in the human neutrophil. The role of anion fluxes in degranulation.

1982 ◽  
Vol 257 (12) ◽  
pp. 6916-6922
Author(s):  
H M Korchak ◽  
B A Eisenstat ◽  
J E Smolen ◽  
L E Rutherford ◽  
P B Dunham ◽  
...  
Keyword(s):  
Human Neutrophil ◽  
Stimulus Response

PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5157-5165 ◽  
Author(s):  
T. Vernoux ◽  
J. Kronenberger ◽  
O. Grandjean ◽  
P. Laufs ◽  
J. Traas
Keyword(s):  
Cell Fate ◽  
Apical Meristem ◽  
Transmembrane Protein ◽  
Loss Of Function ◽  
Hybrid Identity ◽  
Hormone Transport ◽  
Early Markers ◽  
Ideal Tool ◽  
And Function

The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.

Role of different Ca2+ sources in the superoxide production of human neutrophil granulocytes

1999 ◽  
Vol 26 (9-10) ◽  
pp. 1092-1099 ◽  
Author(s):  
Miklós Geiszt ◽  
Júlia B Szeberényi ◽  
Krisztina Káldi ◽  
Erzsébet Ligeti
Keyword(s):  
Human Neutrophil ◽  
Superoxide Production ◽  
Neutrophil Granulocytes

scholarly journals Repression of differentiation genes by Hes transcription factors fuels neural tumour growth in Drosophila

2021 ◽  
Author(s):  
Chrysanthi Voutyraki ◽  
Alexandros Choromidis ◽  
Vasiliki Theodorou ◽  
Christina Efraimoglou ◽  
Gerasimos Anagnostopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Notch Signaling ◽  
Tumour Growth ◽  
Metabolic Reprogramming ◽  
Cell Physiology ◽  
Malignant Tumours ◽  
Rna Profiling ◽  
A Cell

Background: Neural stem cells (NSC) in divide asymmetrically to generate a cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the plethora of neurons and glial cells that wire the brain and nerve cord. Genetic insults, such as excess of Notch signaling, perturb the normal NSC proliferation programs and trigger the formation of NSC hyperplasias, that can later progress to malignancies. Hes proteins are crucial mediators of Notch signaling and in the NSC context they act by repressing a cohort of early pro-differentiation transcription factors. Downregulation of these pro-differentiation factors makes NSC progeny cells susceptible to adopting an aberrant stem cell program. We have recently shown that Hes overexpression in Drosophila leads to NSC hyperplasias that progress to malignant tumours after allografting to adult hosts. Methods: We have combined genetic analysis, tissue allografting and transcriptomic approaches to address the role of Hes genes in NSC malignant transformation. Results: We show that the E(spl) genes are important mediators in the progression of Notch hyperplasias to malignancy, since allografts lacking the E(spl) genes grow much slower. We further present RNA profiling of Hes-induced tumours at two different stages after allografting. We find that the same cohort of differentiation-promoting transcription factors that are repressed in the primary hyperplasias continue to be downregulated after transplantation. This is accompanied by an upregulation of stress-response genes and metabolic reprogramming. Conclusions: The combination of dedifferentiation and cell physiology changes most likely drive tumour growth.

scholarly journals Role of secretory events in modulating human neutrophil chemotaxis.

1978 ◽  
Vol 62 (6) ◽  
pp. 1364-1374 ◽  
Author(s):  
J I Gallin ◽  
D G Wright ◽  
E Schiffmann
Keyword(s):  
Human Neutrophil ◽  
Neutrophil Chemotaxis

scholarly journals Systemic muscle wasting and coordinated tumour response drive tumourigenesis

2019 ◽  
Author(s):  
Holly Newton ◽  
Yi-Fang Wang ◽  
Laura Camplese ◽  
André E.X. Brown ◽  
Susumu Hirabayashi
Keyword(s):  
Amino Acid ◽  
Tumour Growth ◽  
Muscle Wasting ◽  
Human Cancer ◽  
Tumour Response ◽  
Human Kidney ◽  
Amino Acid Derivative ◽  
Database Analysis ◽  
Powerful Approach ◽  
Transporter Expression

SUMMARYCancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network.

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