Normal fibroblasts induce E-cadherin loss and increase lymph node metastasis in gastric cancer.
BACKGROUND
A tumor is considered a heterogeneous complex in a three-dimensional environment that is flush with pathophysiological and biomechanical signals. Cell-stroma interactions guide the development and generation of tumors. Here, we evaluate the contributions of normal fibroblasts to gastric cancer.


RESULTS
By coculturing normal fibroblasts in monolayers of BGC-823 gastric cancer cells, tumor cells sporadically developed short, spindle-like morphological characteristics and demonstrated enhanced proliferation and invasive potential. Furthermore, the transformed tumor cells demonstrated decreased tumor formation and increased lymphomatic and intestinal metastatic potential. Non-transformed BGC-823 cells, in contrast, demonstrated primary tumor formation and delayed intestinal and lymph node invasion. We also observed E-cadherin loss and the upregulation of vimentin expression in the transformed tumor cells, which suggested that the increase in metastasis was induced by epithelial-to-mesenchymal transition.


CONCLUSIONS
Collectively, our data indicated that normal fibroblasts sufficiently induce epithelial-to-mesenchymal transition in cancer cells, thereby leading to metastasis.
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Wen
W
Xu
Department of Orthopedics, Second Affiliated Hospital (Binjiang Branch) of Zhejiang University, School of Medicine, Hangzhou, China.
Xinlei
X
Hu
Department of Pharmacy, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Zhongting
Z
Chen
Department of Pathology, Qujiang People's Hospital, Quzhou, China.
Xiaoping
X
Zheng
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Chenjing
C
Zhang
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Gang
G
Wang
Zhejiang Academy of Traditional Chinese Medicine, Experimental Animal Research Center, Hangzhou, China.
Yu
Y
Chen
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Xinglu
X
Zhou
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Xiaoxiao
X
Tang
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Laisheng
L
Luo
Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch) of Zhejiang University, School of Medicine, Hangzhou, China.
Xiang
X
Xu
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Department of Gastroenterology, Second Affiliated Hospital (Binjiang Branch) of Zhejiang University, School of Medicine, Hangzhou, China.
Wensheng
W
Pan
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
D015820:Cadherins; D009363:Neoplasm Proteins