Soluble CD109 released from lung adenocarcinoma cells activates the STAT3 signaling pathway to promote lymphatic endothelial cell migration
Year: 2026
Type: article
Abstract: Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer, frequently metastasizes to regional lymph nodes through the lymphatic system.CD109 is upregulated in LUAD and is associated with poor prognosis; however, its effects on lymphatic endothelial cells remain poorly characterized.The present study investigated whether soluble CD109 released from LUAD cells influences lymphatic endothelial cell function and explored the underlying molecular mechanisms.CD109 was overexpressed in human LUAD A549 cells using an adenoviral vector.Conditioned medium (CD109-CM) was collected following demonstration of CD109 expression and secretion using reverse transcription-quantitative PCR and western blotting.The effects of soluble CD109 on human dermal lymphatic endothelial cells (HDLECs) were evaluated using proliferation and migration assays.Involvement of the Janus kinase 2 (JAK2)/STAT3 signaling pathway was examined using western blotting and further evaluated using Stattic, a STAT3 inhibitor.CD109 overexpression in A549 cells significantly increased both cellular and secreted CD109 levels.Despite CD109-CM having not significantly affected HDLEC proliferation, it markedly enhanced HDLEC migration.Mechanistically, CD109-CM increased JAK2 and STAT3 phosphorylation in HDLECs, consistent with activation of STAT3 signaling.Pharmacological inhibition of STAT3 signaling with Stattic attenuated STAT3 phosphorylation and abolished the CD109-CM-induced increase in HDLEC migration.Collectively, these findings demonstrated that soluble CD109 released from LUAD cells may promote lymphatic endothelial cell migration through activation of JAK2/STAT3 signaling.The present in vitro findings identified the CD109-JAK2/STAT3 axis as a potential mechanism through which LUAD cells modulate lymphatic endothelial cell behavior, thus supporting further in vivo investigation of CD109 as a potential therapeutic target in LUAD.
Source: Biomedical Reports
DOI: 10.3892/br.2026.2225
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225638112
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