Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.
Anna Durrans1, Dingcheng Gao1, Ravi Gupta2
1Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, United States of America; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, United States of America; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, United States of America.
This study reveals increased bone marrow-derived cells in non-small cell lung cancer (NSCLC) tumors. Analyzing these cells identified novel therapeutic targets like osteopontin, crucial for enhancing lung cancer growth.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
- Despite treatment advancements, patient prognosis for NSCLC is often poor.
- Understanding the molecular mechanisms driving NSCLC, particularly the role of stromal cells, is critical for developing new therapies.
Purpose of the Study:
- To investigate the contribution of bone marrow-derived stromal cells to NSCLC progression.
- To identify novel molecular targets within NSCLC stroma that influence tumor growth and prognosis.
- To explore the therapeutic potential of targeting specific stromal cell populations in NSCLC.
Main Methods:
- Comparison of transcriptomes between intratumoral myeloid compartments and adjacent non-neoplastic lung tissue from NSCLC patients.
- Isolation and RNA sequencing of specific myeloid cell fractions, including immature monocytic myeloid cells and polymorphonuclear neutrophils.
- Analysis of differentially regulated genes and mRNA isoforms in homogeneous stromal populations from fresh clinical specimens.
Main Results:
- Increased numbers of bone marrow-derived hematopoietic cells were observed in NSCLC tumor parenchyma compared to adjacent non-neoplastic lung tissue.
- RNA sequencing identified differentially regulated genes and mRNA isoforms in intratumoral myeloid cells, which were not apparent in whole tumor analyses.
- Key genes encoding secreted factors, such as osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7), and thrombospondin 1 (TSP1), were identified and shown to enhance lung cancer cell tumorigenicity.
Conclusions:
- Analysis of homogeneous stromal populations from fresh NSCLC specimens can reveal crucial stromal genes with therapeutic value.
- Stromal cells, particularly specific myeloid compartments, play a significant role in NSCLC progression.
- Identified genes like OPN, CCL7, and TSP1 represent potential therapeutic targets for NSCLC treatment.
More Related Videos
08:49Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
07:24Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
