WCLC 2025 - Posters & ePosters-P2.02.09 Early-Stage Lung Adenocarcinoma: PLVAP-Driven Regulation of the Tumor Microenvironment

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This study investigates the role of PLVAP-driven tip-like endothelial cells (TECs) in early-stage lung adenocarcinoma (LUAD) and their impact on the tumor microenvironment. Using integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics on human and murine lung tumor samples, the researchers identified TECs as a distinct tumor-associated endothelial subpopulation that likely originates from type I capillaries and is regulated by tumor-derived transforming growth factor beta 1 (TGFβ1) signaling.<br /><br />PLVAP (plasmalemma vesicle-associated protein) emerged as a key marker of TECs and was significantly associated with poor patient prognosis in early LUAD. Functional assays including migration, invasion, tubulogenesis, and tumor-endothelial co-culture demonstrated that PLVAP promotes endothelial invasion, angiogenesis, and tumor metastasis. A reciprocal crosstalk mediated by the PLVAP-TGFβ1 axis between TECs and tumor cells facilitates vascular remodeling and tumor invasiveness during early neovascular infiltration, which drives tumor progression.<br /><br />The study highlights that anti-angiogenic therapies targeting TECs reduce their abundance, but the molecular mechanisms underlying TEC plasticity and gene regulation during early vascular co-option were previously unclear. This work clarifies those mechanisms and suggests that disrupting PLVAP-TGFβ1 signaling could effectively prevent early metastatic niche formation, thereby inhibiting tumor progression and spread.<br /><br />Future research directions include evaluating the therapeutic potential of targeting PLVAP-expressing TECs and their autocrine/paracrine TGFβ1 signaling to suppress angiogenesis and metastasis in early LUAD. This approach could offer a novel strategy to interfere with early tumor–endothelial interactions and improve patient outcomes.<br /><br />Supported by multiple national science foundations and institutions in China and the USA, this research provides critical insights into the vascular regulation of early lung cancer progression and identifies actionable molecular targets for early intervention.

Asset Subtitle

Dawei Yang

Meta Tag

Speaker Dawei Yang

Topic Tumor Biology – Preclinical Biology

Keywords

PLVAP

tip-like endothelial cells

TECs

lung adenocarcinoma

LUAD

tumor microenvironment

TGFβ1 signaling

angiogenesis

tumor metastasis

vascular remodeling