title: Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala Branch, Uppsala, Sweden.
authors.forename: Masao
authors.initials: M
authors.lastname: Furuhashi
authors.forename: Tobias
authors.initials: T
authors.lastname: Sjöblom
authors.forename: Alexandra
authors.initials: A
authors.lastname: Abramsson
authors.forename: Jens
authors.initials: J
authors.lastname: Ellingsen
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Erika
authors.initials: E
authors.lastname: Bergsten-Folestad
authors.forename: Ulf
authors.initials: U
authors.lastname: Eriksson
authors.forename: Rainer
authors.initials: R
authors.lastname: Heuchel
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Heldin
authors.forename: Arne
authors.initials: A
authors.lastname: Ostman
mesh_terms: 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
chemical_list: 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