Characterization of human lung cancer-associated fibroblasts in three-dimensional in vitro co-culture model.
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 α-smooth muscle actin (α-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.
Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Masafumi
M
Horie
Akira
A
Saito
Yu
Y
Mikami
Mitsuhiro
M
Ohshima
Yasuyuki
Y
Morishita
Jun
J
Nakajima
Tadashi
T
Kohyama
Takahide
T
Nagase
D000199:Actins / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002469:Cell Separation; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology; D014407:Tumor Cells, Cultured
C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor