Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate.
Platelet-derived growth factor (PDGF) receptor signaling participates in different processes in solid tumors, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. In the present study, the B16 mouse melanoma tumor model was used to investigate the functional consequences of paracrine PDGF stimulation of host-derived cells. Production of PDGF-BB or PDGF-DD by tumor cells was associated with an increased tumor growth rate. Characterization of tumors revealed an increase in pericyte abundance in tumors derived from B16 cells producing PDGF-BB or PDGF-DD. The increased tumor growth rate associated with PDGF-DD production was not seen in mice expressing an attenuated PDGF beta-receptor and was thus dependent on host PDGF beta-receptor signaling. The increased pericyte abundance was not associated with an increased tumor vessel density. However, tumor cell apoptosis, but not proliferation, was reduced in tumors displaying PDGF-induced increased pericyte coverage. Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth.
Furuhashi
Masao
M
Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, Sweden.
Sjöblom
Tobias
T
Abramsson
Alexandra
A
Ellingsen
Jens
J
Micke
Patrick
P
Li
Hong
H
Bergsten-Folestad
Erika
E
Eriksson
Ulf
U
Heuchel
Rainer
R
Betsholtz
Christer
C
Heldin
Carl-Henrik
CH
Ostman
Arne
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D000077214:Becaplermin; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D008222:Lymphokines; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis
D008222:Lymphokines; C498951:Pdgfd protein, mouse; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta