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Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC
- Source :
- PLoS ONE, Vol 10, Iss 6, p e0129123 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.
- Subjects :
- Pathology
medicine.medical_specialty
Lung Neoplasms
Myeloid
Stromal cell
lcsh:Medicine
Biology
medicine.disease_cause
CCL7
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Biomarkers, Tumor
medicine
Adenocarcinoma of the lung
Animals
Humans
Myeloid Cells
RNA, Messenger
Osteopontin
Chemokine CCL7
lcsh:Science
Lung cancer
Lung
Multidisciplinary
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
lcsh:R
Hematopoietic Stem Cells
medicine.disease
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
medicine.anatomical_structure
biology.protein
lcsh:Q
Bone marrow
Transcriptome
Carcinogenesis
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....6d1b2632b026025ce391f71769b16ace