Low molecular weight heparin suppresses lymphatic endothelial cell proliferation induced by vascular endothelial growth factor C in vitro.
BACKGROUND
Pancreatic cancer is one of the most aggressive human malignancies. Lymphangiogenesis plays an important role in lymph node metastasis of many solid tumors. It is well known that low molecular weight heparins (LMWHs) can inhibit cell growth, cell invasion and angiogenesis, which are key processes in tumor progression.


METHODS
We measured the expression of vascular endothelial growth factor C (VEGF-C) in pancreatic cancer cells (PANC-1) using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. We used an in vitro assay to evaluate the anti-lymphangiogenic effect of an LMWH, Fragmin, on human lymphatic endothelial cell (HLEC) proliferation.


RESULTS
Fragmin at a low concentration can effectively inhibits HLEC proliferation induced by VEGF-C. VEGF-C secreted by PANC-1 cells stimulated HLEC proliferation. Low concentration LMWH suppressed HLEC proliferation induced by VEGF-C but did not affect proliferation or VEGF-C expression of PANC-1 cells, whereas high concentrations of LMWH inhibited PANC-1 cell proliferation.


CONCLUSIONS
These results suggest that VEGF-C released by cancer cells plays an important role in promoting HLEC proliferation. The LMWH Fragmin has anti-lymphangiogenic effects and may inhibit lymphatic metastasis in pancreatic cancer.
Cao
Guang
G
Department of General Surgery, Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Wu
Ji-xiang
JX
Wu
Qing-hua
QH
D000925:Anticoagulants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017985:Dalteparin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*
D000925:Anticoagulants; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D017985:Dalteparin