Cancer Proliferation at the Brain Metastatic Site: A Proteomic Exploration of Inter-Cellular Cross-talk Sustained by Cell-membrane/Secretome Interactions

Brain metastasis of breast cancer is one of the leading causes of mortality in patients suffering from cancer. The unique structure and components of the brain microenvironment, including the brain-blood barrier and the immune-suppressive environment, present significant clinical challenges to treating brain metastatic breast cancers. This study has hypothesized that the thriving of metastatic breast cancer cells within the brain is driven by the complex interactions between cancer cells and the brain tumor microenvironment, which is reshaped into a tumor-permissive environment. Therefore, by utilizing mass spectrometry-based proteomic analysis, this study focused on analyzing the secretome and cell surfaceome of metastatic breast cancer and brain-residential cells to reveal the interactions between these cells and contribution to various cancer-developing biological processes, including cell growth and proliferation, cell death and apoptosis, immune modulation, angiogenesis, extracellular matrix organization, and epithelial-mesenchymal transition. The project was conducted in three tiers: (1) profiling the secreted and cell membrane proteins, (2) mapping ligand-receptor interactions using an in-house ligand-receptor database, and (3) determining the functional roles of the interacting ligands and receptors. The analysis revealed a complex network of intercellular communications demonstrating how the cancer cells could potentially influence the brain residential cells and, conversely, how the brain cells could influence the cancer cells and contribute to reshaping the tumor microenvironments to support cancer progression. 3D co-culture spheroid models further underlined the influence of cell-cell interactions on tumor growth. Altogether, this work provides an integrated approach to understanding the molecular cross-talk within the brain tumor microenvironment and in-depth insights into potential therapeutic targets to disrupt tumor-promoting changes in the brain metastatic niche.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biological Sciences

Department dc:contributor.department

Biological Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2025

Author dc:creator

• Zhang, Yunqian

Chair dc:contributor.committeechair

• Lazar, Maria Iuliana

Committee members dc:contributor.committeemember

• Hsu, Bryan
• Lamouille, Samy
• Li, Liwu

• Proteomics
• Mass spectrometry
• Breast cancer
• Secretome
• Cell membrane
• Brain metastasis
• Tumor microenvironment
• Intercellular communication

Statement dc:rights

• Creative Commons Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:42445

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/124295