PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.
Cancer metastases are commonly found in the lymphatic system. Like tumor blood angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of several tumor-derived growth factors. Here we report that members of the PDGF family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF-BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.
Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden.
Renhai
R
Cao
Meit A
MA
Björndahl
Piotr
P
Religa
Steve
S
Clasper
Stina
S
Garvin
Dagmar
D
Galter
Björn
B
Meister
Fumitaka
F
Ikomi
Katerina
K
Tritsaris
Steen
S
Dissing
Toshio
T
Ohhashi
David G
DG
Jackson
Yihai
Y
Cao
D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects*; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor