Extracellular vesicles from non-neuroendocrine SCLC cells promote adhesion and survival of neuroendocrine SCLC cells

Lizandra Jimenez; Victor Stolzenbach; Patricia M M Ozawa; Marisol Ramirez-Solano; Qi Liu; Julien Sage; Alissa M Weaver

doi:10.1002/pmic.202300030

Extracellular vesicles from non-neuroendocrine SCLC cells promote adhesion and survival of neuroendocrine SCLC cells

Proteomics. 2023 Nov 5:e2300030. doi: 10.1002/pmic.202300030. Online ahead of print.

Authors

Lizandra Jimenez^{1

2}, Victor Stolzenbach^{1

2}, Patricia M M Ozawa^{1

2}, Marisol Ramirez-Solano³, Qi Liu³, Julien Sage^{4

5}, Alissa M Weaver^{1

2

6}

Affiliations

¹ Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
² Center for Extracellular Vesicle Research, Vanderbilt University, Nashville, Tennessee, USA.
³ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁴ Department of Pediatrics, Stanford Medicine, Stanford, California, USA.
⁵ Department of Genetics, Stanford Medicine, Stanford, California, USA.
⁶ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

PMID: 37926756
DOI: 10.1002/pmic.202300030

Abstract

Small cell lung cancer (SCLC) tumors are made up of distinct cell subpopulations, including neuroendocrine (NE) and non-neuroendocrine (non-NE) cells. While secreted factors from non-NE SCLC cells have been shown to support the growth of the NE cells, the underlying molecular factors are not well understood. Here, we show that exosome-type small extracellular vesicles (SEVs) secreted from non-NE SCLC cells promote adhesion and survival of NE SCLC cells. Proteomic analysis of purified SEVs revealed that extracellular matrix (ECM) proteins and integrins are highly enriched in SEVs of non-NE cells whereas nucleic acid-binding proteins are enriched in SEVs purified from NE cells. Addition of select purified ECM proteins identified in purified extracellular vesicles (EVs), specifically fibronectin, laminin 411, and laminin 511, were able to substitute for the role of non-NE-derived SEVs in promoting adhesion and survival of NE SCLC cells. Those same proteins were differentially expressed by human SCLC subtypes. These data suggest that ECM-carrying SEVs secreted by non-NE cells play a key role in supporting the growth and survival of NE SCLC cells.

Keywords: ECM; SCLC; extracellular vesicles; proteomics; tumor heterogeneity.

Abstract

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