Cancer cell-derived IL-1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells.
OBJECTIVE
Interleukin (IL)-1α and hepatocyte growth factor (HGF) play an important role in pancreatic cancer proliferation, angiogenesis, and invasiveness. The aim of this study was to investigate the cooperative role of HGF and IL-1α in metastatic processes promoted by interactions between pancreatic cancer cells and stromal cells.


METHODS
Expression of IL-1α and HGF mRNA and protein was determined by RT-PCR and ELISA. The effect of HGF on metastatic potential was evaluated by proliferation, invasion, and angiogenesis assays using an in vitro system consisting of co-cultured tumor cells and stromal cells.


RESULTS
IL-1α expression was closely correlated with metastatic potential, and cancer cell-derived IL-1α significantly promoted HGF expression by fibroblasts (P < 0.01). HGF not only enhanced the invasiveness and proliferation of pancreatic cancer cells, but also enhanced migration and proliferation of human umbilical vein endothelial cells (HUVECs). HGF significantly enhanced HUVEC tube formation (P < 0.01). Furthermore, the high liver-metastatic pancreatic cancer cell line (BxPC-3), which secretes IL-1α, significantly enhanced HUVEC tube formation compared with the low liver-metastatic cell line (Capan-2), which does not produce IL-1α (P < 0.01).


CONCLUSIONS
Autocrine IL-1α and paracrine HGF co-enhance the metastatic potential of pancreatic cancer cells via both IL-1α and HGF signaling pathways.
Xu
Donghui
D
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, Mizuhoku, Nagoya, Japan.
Matsuo
Yoichi
Y
Ma
Jiachi
J
Koide
Shuji
S
Ochi
Nobuo
N
Yasuda
Akira
A
Funahashi
Hitoshi
H
Okada
Yuji
Y
Takeyama
Hiromitsu
H
D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
D053582:Interleukin-1alpha; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor