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Title: Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model

Abstract

Highlights: Black-Right-Pointing-Pointer We established three patient-paired sets of CAFs and NFs. Black-Right-Pointing-Pointer CAFs and NFs were analyzed using three-dimensional co-culture experiments. Black-Right-Pointing-Pointer CAFs clearly enhanced collagen gel contraction. Black-Right-Pointing-Pointer CAFs showed higher {alpha}-SMA expression than NFs. Black-Right-Pointing-Pointer CAFs were implicated in invasion and differentiation of lung cancer cells. -- Abstract: Lung cancer is the most common cause of cancer-related death worldwide. Stromal cancer-associated fibroblasts (CAFs) play crucial roles in carcinogenesis, proliferation, invasion, and metastasis of non-small cell lung carcinoma, and targeting of CAFs could be a novel strategy for cancer treatment. However, the characteristics of human CAFs still remain to be better defined. In this study, we established patient-matched CAFs and normal fibroblasts (NFs), from tumoral and non-tumoral portions of resected lung tissue from lung cancer patients. CAFs showed higher {alpha}-smooth muscle actin ({alpha}-SMA) expression than NFs, and CAFs clearly enhanced collagen gel contraction. Furthermore, we employed three-dimensional co-culture assay with A549 lung cancer cells, where CAFs were more potent in inducing collagen gel contraction. Hematoxylin and eosin staining of co-cultured collagen gel revealed that CAFs had the potential to increase invasion of A549 cells compared to NFs. These observations provide evidence that lung CAFs have the tumor-promoting capacity distinctmore » from NFs.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [4]; ;  [1]
  1. Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo (Japan)
  2. Department of Biochemistry, Ohu University School of Pharmaceutical Sciences (Japan)
  3. Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo (Japan)
  4. Department of Thoracic Surgery, Graduate School of Medicine, University of Tokyo (Japan)
Publication Date:
OSTI Identifier:
22207908
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 423; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; CARCINOGENESIS; CARCINOMAS; CATTLE; CELL PROLIFERATION; COLLAGEN; EOSIN; FIBROBLASTS; HEMATOXYLIN; IN VITRO; LUNGS; METASTASES; MUSCLES; PATIENTS

Citation Formats

Horie, Masafumi, Saito, Akira, E-mail: asaitou-tky@umin.ac.jp, Mikami, Yu, Ohshima, Mitsuhiro, Morishita, Yasuyuki, Nakajima, Jun, Kohyama, Tadashi, and Nagase, Takahide. Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.05.104.
Horie, Masafumi, Saito, Akira, E-mail: asaitou-tky@umin.ac.jp, Mikami, Yu, Ohshima, Mitsuhiro, Morishita, Yasuyuki, Nakajima, Jun, Kohyama, Tadashi, & Nagase, Takahide. Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model. United States. doi:10.1016/J.BBRC.2012.05.104.
Horie, Masafumi, Saito, Akira, E-mail: asaitou-tky@umin.ac.jp, Mikami, Yu, Ohshima, Mitsuhiro, Morishita, Yasuyuki, Nakajima, Jun, Kohyama, Tadashi, and Nagase, Takahide. Fri . "Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model". United States. doi:10.1016/J.BBRC.2012.05.104.
@article{osti_22207908,
title = {Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model},
author = {Horie, Masafumi and Saito, Akira, E-mail: asaitou-tky@umin.ac.jp and Mikami, Yu and Ohshima, Mitsuhiro and Morishita, Yasuyuki and Nakajima, Jun and Kohyama, Tadashi and Nagase, Takahide},
abstractNote = {Highlights: Black-Right-Pointing-Pointer We established three patient-paired sets of CAFs and NFs. Black-Right-Pointing-Pointer CAFs and NFs were analyzed using three-dimensional co-culture experiments. Black-Right-Pointing-Pointer CAFs clearly enhanced collagen gel contraction. Black-Right-Pointing-Pointer CAFs showed higher {alpha}-SMA expression than NFs. Black-Right-Pointing-Pointer CAFs were implicated in invasion and differentiation of lung cancer cells. -- Abstract: Lung cancer is the most common cause of cancer-related death worldwide. Stromal cancer-associated fibroblasts (CAFs) play crucial roles in carcinogenesis, proliferation, invasion, and metastasis of non-small cell lung carcinoma, and targeting of CAFs could be a novel strategy for cancer treatment. However, the characteristics of human CAFs still remain to be better defined. In this study, we established patient-matched CAFs and normal fibroblasts (NFs), from tumoral and non-tumoral portions of resected lung tissue from lung cancer patients. CAFs showed higher {alpha}-smooth muscle actin ({alpha}-SMA) expression than NFs, and CAFs clearly enhanced collagen gel contraction. Furthermore, we employed three-dimensional co-culture assay with A549 lung cancer cells, where CAFs were more potent in inducing collagen gel contraction. Hematoxylin and eosin staining of co-cultured collagen gel revealed that CAFs had the potential to increase invasion of A549 cells compared to NFs. These observations provide evidence that lung CAFs have the tumor-promoting capacity distinct from NFs.},
doi = {10.1016/J.BBRC.2012.05.104},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 423,
place = {United States},
year = {2012},
month = {6}
}