Dataset Information

Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma

ABSTRACT: Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tu-mor cells, CTCs) either alone or Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tu-mor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell–cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tis-sue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on com-panion cells in clusters.as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell–cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tis-sue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on com-panion cells in clusters.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Circulating Cell

DISEASE(S): Pancreatic Carcinoma

SUBMITTER: Harrys Kishore Charles Jacob

LAB HEAD: Ashok Saluja

PROVIDER: PXD026340 | Pride | 2021-06-07

REPOSITORIES: Pride

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Publications

Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma.

Charles Jacob Harrys Kishore HK Charles Richard John Lalith JL Signorelli Rossana R Kashuv Tyler T Lavania Shweta S Vaish Utpreksha U Boopathy Ranjitha R Middleton Ashley A Boone Melinda Minucci MM Sundaram Ramakrishnan R Dudeja Vikas V Saluja Ashok Kumar AK

Cancers 20210531 11

Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell-cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for a ...[more]

PMID: 34072942

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Project description:MicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We now demonstrate that endogenous and over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). We report that the "seed region" of moR-21 as well as the "seed match region" in the target gene 3'UTR are indispensable for moR-21-mediated gene down-regulation. We further demonstrated that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. Taken together, these findings provide the first evidence that microRNA offset RNA regulates gene expression and is biologically active. Small RNAs were harvested from mouse aortic smooth muscle cells (AoSMCs), with three biological replicates, using miReasy kits (Qiagen) according to the manufacturerâ??s instructions. RNA was quantified using a Nanodrop spectrophotometer. Small RNA library construction and illumina HiSeq 75bp single read sequencing were performed at the Yale Center for Genome Analysis. Reads were trimmed to remove adaptor sequences, and inserts longer than 13 bases were mapped to the mouse mm10 genome using Bowtie (with settings â??n 0 -m 5 --best --strata, allowing 0 mismatches and up to 5 genomic loci with a perfect match, {Genome Biol. 2009;10(3):R25, Langmead B, Trapnell C, Pop M, Salzberg SL}). Reads that mapped to within 50 bp of more than one annotated mouse pri-miR (as defined by miRBase {Kozomara A, Griffiths-Jones S. Nucelic Acids Res 2014 42:D68-D73}), were allotted evenly between these locations. Reads that fell entirely within established miRbase 3p or 5p miR coordinates, plus or minus 3 bp, were counted as 3p or 5p miRs, respectively. Reads that fell entirely within the range of 35 bp 3â?? to 3 bp 5â?? of the last base of a 3p miR were counted as 3p moR reads. Those that fell entirely between 3bp 3â?? and 35 bp 5â?? of the first base of a 5p miR were counted as 5p moR reads. On average each library contained 17.4 million qualifying inserts, of which 13.8 million (79.3%) mapped to one of these four regions, indicating that the large majority of inserts represented miR or moR sequences. Reads were divided by the number of million reads mapping to these regions in each library to give normalized reads per million reads (RPMR) values.

Dataset Information

Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma

Publications

Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma.

Similar Datasets

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