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Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and function.
- Source :
-
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2014 May; Vol. 9 (5), pp. 664-74. - Publication Year :
- 2014
-
Abstract
- Background: Cancer-associated stromal cells interact with carcinoma cells and thus participate in tumor growth. Our aim was to characterize the ultrastructure and contractile properties of stromal cells in collagen gel cultured from lung cancer of various histological types and from tumor-free lung.<br />Methods: Cells cultured from lung cancer (13 adenocarcinomas, six squamous cell carcinomas, one adenosquamous carcinoma, and one pleomorphic carcinoma) and tumor-free lung were analyzed by transmission electron microscopy and three-dimensional collagen gel contraction assays. The expression of α-smooth muscle actin (α-SMA), a recognized myofibroblast marker, was examined by immunoelectron microscopy from individual cells and by Western blotting from the whole cultured cell population.<br />Results: According to their ultrastructure, the cell lines were composed of fibroblastic and myofibroblastic cells. In electron microscopy, cells of lung cancer exhibited more myofibroblastic features displaying higher amounts of actin belts (p = 0.057) and α-SMA labeling (p = 0.010) than cells from tumor-free lung. Myofibroblasts cultured from lung cancer of smokers expressed less α-SMA labeling (p = 0.013) than counterparts from nonsmokers. Western blotting revealed that cancer-associated fibroblasts expressed more α-SMA (p = 0.006) than cells from tumor-free lung, whereas cells from tumor-free central lung of smokers showed less α-SMA (p = 0.039) than counterparts from nonsmokers. Cells cultured from cancer contracted more in collagen gel than those from tumor-free lung. The contractile capacity in collagen gel correlated with the frequency of extracellular component of fibronexus by transmission electron microscopy.<br />Conclusions: Lung cancer-associated myofibroblasts are different both ultrastructurally and functionally when compared with cells cultured from tumor-free lung. Smoking altered myofibroblastic phenotype, regardless of their origin.
- Subjects :
- Actins analysis
Adenocarcinoma physiopathology
Adherens Junctions ultrastructure
Aged
Aged, 80 and over
Carcinoma, Adenosquamous physiopathology
Carcinoma, Squamous Cell physiopathology
Endoplasmic Reticulum, Rough ultrastructure
Extracellular Matrix ultrastructure
Female
Humans
Lung chemistry
Lung physiology
Lung ultrastructure
Lung Neoplasms chemistry
Lung Neoplasms physiopathology
Male
Microscopy, Electron, Transmission
Middle Aged
Myofibroblasts chemistry
Myofibroblasts physiology
Smoking
Tumor Cells, Cultured
Adenocarcinoma ultrastructure
Carcinoma, Adenosquamous ultrastructure
Carcinoma, Squamous Cell ultrastructure
Lung Neoplasms ultrastructure
Myofibroblasts ultrastructure
Subjects
Details
- Language :
- English
- ISSN :
- 1556-1380
- Volume :
- 9
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 24662457
- Full Text :
- https://doi.org/10.1097/JTO.0000000000000149