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O12 - Lung Cancer Biology II (ID 87)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:Y. Nakanishi, B. Solomon
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside 110 A+B, Level 1
O12.01 - Prospective isolation of human lung stem/progenitor cells and their role in the initiation of lung cancer (ID 1716)
10:30 - 12:00 | Author(s): C.E. Weeden
Cells of origin of cancers acquire the first genetic aberration(s) that lead to tumourigenesis. An understanding of the cell of origin in different subtypes of lung cancer could allow earlier detection of malignancies and more effective treatment. Stem or progenitor cells are likely tumour initiating cells due to both their longevity, allowing for accumulation of genetic lesions, and their capacity for renewal. This study aims to isolate human lung progenitor subpopulations based on their differential expression of cell surface markers to evaluate their role as the cell of origin of the different subtypes of lung cancer.
Single cell suspensions were generated from adjacent normal tissue of patients undergoing lung cancer resection. Epithelial cells were immediately separated based on their expression of cell surface markers by fluorescence activated cell sorting (FACS). The progenitor cell capacity of epithelial cell subsets was then assessed using an in vitro colony forming assay. Subsets with progenitor activity were analysed for their expression of differentiated lung cell markers both before and after colony formation.
We have identified a sort strategy that allows for enrichment of basal cells, Clara cells, type I and II pneumocytes from fresh human lung tissue as shown by qPCR and electron microscopy data. The basal cell and type II pneumocyte subpopulations consistently formed colonies in vitro - cell types that have previously shown progenitor activity in the mouse lung. The Clara cell and type I cell compartment did not consistently form colonies. Basal and type II cells formed phenotypically distinct colonies when cultured in a three-dimension matrix that expressed different lung specific markers (p63, SP-C…) as shown by RT-PCR analysis and immunofluorescence staining.
This study has demonstrated the prospective isolation of four epithelial cell subsets from fresh human lung tissue for the first time and confirmed the progenitor activity of basal cells and type II cells in the human lung. We are currently comparing the genetic profile of these human lung progenitor cells with the genetic profile of molecular subtypes of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) using next generation sequencing. Future studies aim to transform lung progenitor cells with genetic alterations common in NSCLC and SCLC to further establish their role as cells of origin of these cancers.
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