DOI: 10.5281/zenodo.18349614
title: IL-1β/CXCL12 signalling orchestrates adipocyte–pancreatic neuroendocrine tumor crosstalk

description: The aim of this study is to investigate whether pancreatic neuroendocrine tumors (PanNETs) are capable of influencing adipocyte dedifferentiation in CAAs.

All data included here support the figures and analyses reported in the corresponding publication.

 

Corresponding Author. Email: giovanni.vitale@unimi.it

 

Data Format and Structure

The dataset is organized into Excel (.xlsx) files, each corresponding to a specific experimental theme or analysis.Each file may contain multiple worksheets, representing data displayed in different figures of the published article.

The files include both raw measurements and processed values (e.g., normalized absorbance, blank-subtracted values, relative expression levels).All data are annotated and include units and sample identifiers where applicable.

 

File Description

File 1 - “OIL_RED_O.xlsx”

This file compiles all results from Oil Red O staining experiments, used to quantify lipid accumulation in adipocytes.These data correspond to Figure 1b, Figure 1e, Figure 5a, and Figure 6a of the article.

The first worksheet contains data associated with Figure 1b, followed by worksheets corresponding to subsequent figures.Each worksheet reports absorbance values measured at 540 nm.

File 2 - “GLYCEROL_RELEASE.xlsx”

This file includes the data presented in Figure 1c, Figure 1f, Figure 5b, and Figure 6b of the article. The first worksheet contains the data used to generate Figure 1c.The second worksheet compiles all remaining data corresponding to Figures 1f, 5b, and 6b.

These data refer to adipocytes exposed to M-tumors or subjected to co-culture experiments, including conditions with AMD3100 and Canakinumab treatments.

The file reports absorbance values obtained following the protocol described in Section 2.7 of the article. 

From these measurements, the corresponding glycerol concentrations (ng/μL) were calculated, and fold changes were then computed relative to the most appropriate control condition.

 

File 3 - “ADIPOCYTE_MARKERS_RTqPCR.xlsx” 

This file contains all data related to the expression of genes identified as reliable markers of adipocyte differentiation.

The file is divided into four worksheets, each corresponding to a specific figure in the article, specifically Figure 1d and g, Figure 2f, Figure 5c and d, Figure 6c and d.Within each worksheet, the number of independent biological experiments used to generate the statistical analysis shown in the corresponding figure is clearly indicated. These data refer to adipocytes exposed to M-tumors or subjected to co-culture experiments, including conditions with AMD3100 and Canakinumab treatments.

Gene expression data are reported as normalized values, first normalized to the housekeeping gene GAPDH and subsequently to the control condition, which for each experiment corresponds to adipocytes cultured alone.

Gene expression analysis of adipocyte markers was performed by real-time PCR (RT-qPCR).Each parameter is provided in a dedicated file, following the same structure and annotation scheme adopted throughout the dataset.

 

 

File 4 - “CELL_COUNT_BON-1_QGP-1_FIBROBLASTS.xlsx”

This file includes the data presented in Figure 3d of the article.

Each worksheet corresponds to a single biological experiment, organized to include cell counts for both BON-1 and QGP-1 cells.For each experiment, data are reported for cells grown in monoculture (serving as growth controls) and in co-culture conditions.

 

File 5 - “CELL_COUNT_BON-1_Co-CULTURED.xlsx”

This file includes the data presented in Figure 3c (BON-1 cells, left panel) of the article and Figure 7b and Figure 7e.

Each worksheet corresponds to a single biological experiment, organized to include cell counts for BON-1 cells.For each experiment, data are reported for cells grown in monoculture (serving as growth controls) and in co-culture conditions, either untreated or treated with AMD3100 and Canakinumab.

 

File 6 - “CELL_COUNT_QGP-1_Co-CULTURED.xlsx”

This file includes the data presented in Figure 3c (QGP-1 cells, right panel) of the article and Figure 7c and Figure 7f.

Each worksheet corresponds to a single biological experiment, organized to include cell counts for QGP-1 cells.For each experiment, data are reported for cells grown in monoculture (serving as growth controls) and in co-culture conditions, either untreated or treated with AMD3100 and Canakinumab.

 

File 7 - “ELISA_IL1beta_CXCL12.xlsx”

This file includes the data presented in Figure 4 of the article. The first worksheet contains the ELISA results for IL-1β,

while the second worksheet compiles the ELISA data for CXCL12.Each worksheet also includes the standard calibration curve used as the reference for the ELISA quantification.

 

File 8 - “MTT_drugs.xlsx”

This file includes the data presented in Supplementary Figure 1 and Figure 7a and Figure 7d of the article.The experiments were performed to determine the drug concentrations to be used in subsequent assays, using the MTT viability assay (Supplementary 1).

The first worksheet contains data for QGP-1 cells treated with AMD3100, both under standard growth conditions and in co-culture with M-AD. The second worksheet includes corresponding data for BON-1 cells treated with AMD3100.The third and fourth worksheets report data for Canakinumab treatments, for QGP-1 and BON-1 cells, respectively.

 

File 9 - “CELL_COUNT_BON-1_QGP-1_M-3T3L1.xlsx”

This file includes the data presented in Figure 3b of the article, for both BON-1 and QGP-1 cells treated with M-3T3L1.

Each worksheet corresponds to a single biological experiment, reporting the results of the proliferation assays performed under the indicated experimental conditions.

 

File 10 - “CELL_COUNT_BON-1_M-AD.xlsx”

This file includes the data presented in Figure 3b of the article, for both BON-1 cells treated with M-AD.

Each worksheet corresponds to a single biological experiment, reporting the results of the proliferation assays performed under the indicated experimental conditions.

 

File 11 - “CELL_COUNT_QGP-1_M-AD.xlsx”

This file includes the data presented in Figure 3b of the article, for both QGP-1 cells treated with M-AD.

Each worksheet corresponds to a single biological experiment, reporting the results of the proliferation assays performed under the indicated experimental conditions.

 

File 12 - “Zebrafish.xlsx”

This file includes the data presented in Supplementary Figure 2 of the article.These experiments were designed to investigate whether BON-1 and QGP-1 cells are able to induce the formation of new blood vessels in vivo, specifically using a zebrafish xenograft model. The file lists the experimental groups used in the study and reports the raw data on which the statistical analyses presented in the article were performed.

Data details: 

column 1 date of the experiments

column 2 name of the experimental group

column 3 area measured in number of pixel

column 4 normalized area; in each experiment area values were normalized on the average of area in embryos injected with monoculture

column 5 average of normalized area in each experimental group

 

File 13 - “CAA_analysis.xlsx”

This file includes the data presented in Figure 2 of the article. These experiments were designed to characterize the identity of the cells composing adipocyte samples grown in monoculture or in co-culture with BON-1 or QGP-1 cells. The file lists the experimental groups used in the study and reports the raw data on which the statistical analyses presented in the article were performed.

 

Data available upon reasonable request. 
description: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms belonging to the broader group of neuroendocrine neoplasms. Epidemiological evidence indicates that visceral obesity is associated with both an increased incidence of PanNETs and unfavorable clinicopathological features. However, the mechanisms underlying adipocyte– PanNETs interactions remain poorly understood.

Here, we investigated the crosstalk between adipocytes and PanNETs cells (BON-1 and QGP-1 cell lines) using indirect co-culture systems and conditioned media derived from differentiated 3T3-L1 adipocytes or PanNETs cells. Our results demonstrate that PanNETs cells induce adipocyte reprogramming toward a cancer-associated adipocyte (CAA) phenotype, characterized by lipid depletion and downregulation of adipogenic markers, including Pparg, Fabp4, Hsl, and Atgl. 

We identified PanNET-derived interleukin-1β (IL-1β) as a key driver of adipocyte conversion into CAAs. This process was accompanied by increased secretion of the chemokine CXCL12 from CAAs, which in turn enhanced PanNET cell proliferation and IL-1β release, thereby establishing a positive feedback loop between CXCL12 and IL-1β in CAAs and PanNET cells, respectively. Pharmacological disruption of this axis using AMD3100, a CXCR4 antagonist, significantly reduced both IL-1β and CXCL12 secretion, prevented adipocyte reprogramming, and suppressed tumor cell proliferation. Comparable effects were observed following incubation of PanNET–adipocyte co-cultures with canakinumab, an IL-1β pathway inhibitor. Collectively, these findings identify IL-1β and CXCL12 as critical mediators of the inflammatory crosstalk between adipocytes and PanNET cells. Targeting this signalling axis may therefore represent a promising therapeutic strategy for PanNETs.