PuSH - Publication Server of Helmholtz Zentrum München: Targeting fibroblast-endothelial interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Koc-Gunel, S.* ; Liu, E.C.* ; Gautam, L.K.* ; Calvert, B.A.* ; Murthy, S.* ; Harriott, N.C.* ; Nawroth, J. ; Zhou, B.* ; Krymskaya, V.P.* ; Ryan, A.L.*

Targeting fibroblast-endothelial interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics.

JCI insight 10:e187899 (2025)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

Lymphangioleiomyomatosis (LAM) is a progressive lung disease with limited treatments, largely due to an incomplete understanding of its pathogenesis. Lymphatic endothelial cells (LECs) invade LAM cell clusters, which include HMB-45-positive epithelioid cells and smooth muscle α-actin-expressing LAM-associated fibroblasts (LAMFs). Recent evidence shows that LAMFs resemble cancer-associated fibroblasts, with LAMF-LEC interactions contributing to disease progression. To explore these mechanisms, we used spatial transcriptomics on LAM lung tissues and identified a gene cluster enriched in kinase signaling pathways linked to myofibroblasts and co-expressed with LEC markers. Kinase arrays revealed elevated PDGFR and FGFR in LAMFs. Using a 3D co-culture spheroid model of primary LAMFs and LECs, we observed increased invasion in LAMF-LEC spheroids compared to non-LAM fibroblasts. Treatment with sorafenib, a multikinase inhibitor, significantly reduced invasion, outperforming Rapamycin. We also confirmed TSC2-deficient renal angiomyolipoma cells (TSC2-null AML) as key VEGF-A secretors, which was suppressed by sorafenib in both TSC2-null AML cells and LAMFs. These findings highlight VEGF-A and bFGF as potential therapeutic targets and suggest multikinase inhibition as a promising strategy for LAM.

Impact Factor

Scopus SNIP

Altmetric

6.100

0.000