title: Human lung cancer-associated fibroblasts enhance motility of non-small cell lung cancer cells in co-culture.
abstract: The metastatic potential of non-small cell lung cancer (NSCLC) cells has been shown to be associated with the tumor microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment, regulating tumor cell function by secreting growth factors, chemokines, and extracellular matrix (ECM). In this study, we examined the role of CAFs in the tumor progression of NSCLC. Firstly, we established primary cultures of CAFs and matched normal fibroblasts (NFs) from patients with resected NSCLC. CAFs exhibited greater expression of the pan-mesenchymal marker α-smooth muscle actin (α-SMA) than did NFs, although they displayed similar morphology. Furthermore, we employed a direct co-culture assay with human NSCLC A549 and H358 cells, and found that CAFs were more potent in inducing the epithelial-to-mesenchymal transition (EMT) phenotype than NFs, as indicated by an elongated and disseminated appearance. CAF-induced EMT led to an increase in motility and a decrease in proliferation of NSCLC cells through SMAD family number-3 (SMAD3)-dependent up-regulation of the growth inhibitory gene p21(CIP1) [cyclin-dependent kinase inhibitor-1A (CDKN1A)] and α-SMA. Taken together, these findings provide evidence that lung CAFs have tumor-promoting capacity distinct from NFs and might play a significant role in the metastatic potential of NSCLC.
authors: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors: Sung-Hyun
authors: SH
authors: Kim
authors: Chungyoul
authors: C
authors: Choe
authors: Yong-Sung
authors: YS
authors: Shin
authors: Mi-Jin
authors: MJ
authors: Jeon
authors: So-Jung
authors: SJ
authors: Choi
authors: Jinseon
authors: J
authors: Lee
authors: Gab-Yong
authors: GY
authors: Bae
authors: Hyuk-Jin
authors: HJ
authors: Cha
authors: Jhingook
authors: J
authors: Kim
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014945:Wound Healing
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: Cancer-associated fibroblasts; EMT; NFs; NSCLC; SMAD3; co-culture; lung cancer; normal fibroblasts; proliferation