Poster H5 - Increased Migration of Lung Adenocarcinoma Brain Metastases is Observed in the Presence of Neurotransmitters

Thursday, October 24, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Jonathan D. French

Undergraduate Researcher
University of Florida
Cantonment, Florida, United States

Co-Author(s)

SC

Sampada Chande

Associate Research Scientist
Yale School of Medicine Department of Pathology, United States

Primary Investigator(s)

DN

Don Nguyen

Associate Research Scientist
Yale School of Medicine Department of Pathology, United States

Introduction: High mortality rates due to brain metastases in non-small cell lung cancer (NSCLC) present a major clinical challenge (1). Lung adenocarcinoma (LUAD) is the most common type of NSCLC (2), with brain metastasis occurring in 30-50% of cases (1). The brain’s neurotransmitters create a unique tumor microenvironment, yet their effects on LUAD cells remain understudied. We previously established that the LUAD cell line H2030-BrM3, selected for brain-specific metastasis, expresses brain-derived neurotrophic factor (BDNF) and glycine receptors (3). This study investigates the migratory and proliferative effects of BDNF and glycine on H2030-BrM3 cells and visualizes neuronal-tumor cell synaptic connections.

1. Y Zhao et al. A novel risk signature for predicting brain metastasis in patients with lung adenocarcinoma. Neuro-Oncology. June 2023
2. What is lung cancer?. American Cancer Society. 29 January 2024
3. E Wingrove et al. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis, Cell Reports. 23 April 2019

Materials and

Methods: Conditions of interest included 30, 50 ng/mL BDNF and 1.0, 1.5 mM glycine, diluted in neurobasal-A (NB) medium. Neuron-conditioned media (CM) were collected at 24 and 72 hours. Wound healing assays measured cell migration from 0 to 24 hours. Proliferation was assessed using a luciferase assay after 5 days. Immunofluorescence staining with Synapsin and Green Fluorescent Protein (GFP) identified synapses and tumor cells.

Results, Conclusions, and Discussions: Significant migratory effects were observed with BDNF (P <.0001 for 50 ng/mL; P=.0009 for 30 ng/mL), glycine (P=.0046 for 1.5 mM; P=.0192 for 1.0 mM), and 72-hour CM (P=.0057). No significant proliferative effects were noted. Immunofluorescence confirmed neuronal-tumor cell synaptic connections. BDNF and glycine induced H2030-BrM3 cell migration within 24 hours, suggesting their potential role in vivo. The 72-hour CM also promoted migration, indicating other neurotransmitters' influence on LUAD cells. The lack of significant proliferation may be due to the NB medium’s neuronal optimization.

Acknowledgements (Optional):