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| Status |
Public on May 16, 2024 |
| Title |
Microenvironment Shapes Small Cell Lung Cancer Neuroendocrine States and Presents Therapeutic Opportunities [DMS273 SCLC cell lines] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Together, our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.
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| Overall design |
DMS273 SCLC cell lines treated with Vehicle (control) and Erdafitinib (Pan-FGFR inhibitor) at 33.33 micromolar concentration for 5 days followed by RNA-seq analysis
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| Contributor(s) |
Parth D, Anish T, Rajesh K |
| Citation(s) |
38897168 |
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| Submission date |
May 15, 2024 |
| Last update date |
Aug 16, 2024 |
| Contact name |
Anish Thomas |
| E-mail(s) |
anish.thomas@nih.gov
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| Organization name |
National Institutes of Health
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| Department |
National Cancer Institute
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| Lab |
Developmental Therapeutics Branch
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| Street address |
Center for Cancer Research, National Cancer Institute, Building 10 Room 4-5330
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| City |
Bethesda |
| State/province |
MARYLAND |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (8)
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| GSM8268908 |
DMS273, Control, rep 4 |
| GSM8268909 |
DMS273, Erda, rep 5 |
| GSM8268910 |
DMS273, Erda, rep 6 |
| GSM8268911 |
DMS273, Erda, rep 7 |
| GSM8268912 |
DMS273, Erda, rep 8 |
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| Relations |
| BioProject |
PRJNA1111856 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267560_RNAseq_Erdafitinib_cell_lines_Normalized.xlsx |
3.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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