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...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 64; no. 8; pp. 2725 - 2733
Main Authors:	FURUHASHI, Masao, SJÖBLOM, Tohias, HELDIN, Carl-Henrik, ÖSTMAN, Arne, ABRAMSSON, Alexandra, ELLINGSEN, Jens, MICKE, Patrick, HONG LI, BERGSTEN-FOLESTAD, Erika, ERIKSSON, Ulf, HEUCHEL, Rainer, BETSHOLTZ, Christer
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-04-2004
Subjects:	alpha-receptor angiogenesis in-vitro Animals Antineoplastic agents Apoptosis - physiology Biological and medical sciences Cancer and Oncology Cancer och onkologi Cell Division - physiology Cell Line, Tumor dermatofibrosarcoma protuberans endothelial-cells Endothelium, Vascular - metabolism Endothelium, Vascular - pathology factor-b healing wounds inhibition Lymphokines Medical sciences Medicin och hälsovetenskap Melanoma, Experimental - blood supply Melanoma, Experimental - metabolism Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology pdgf-beta-receptor Pharmacology. Drug treatments Platelet-Derived Growth Factor - biosynthesis protease-activated ligand Proto-Oncogene Proteins c-sis Receptor, Platelet-Derived Growth Factor beta - biosynthesis recruitment Tumors Pericyte Vertebrata Mammalia Mouse Growth rate Tumor growth B16-Melanoma Spontaneous Rodentia Malignant tumor Platelet derived growth factor Cell Line Research Support Melanoma Pathologic/metabolism/pathology Vascular/metabolism/pathology Inbred C57BL Endothelium Experimental/blood supply/metabolism/pathology Receptor Tumor Platelet-Derived Growth Factor beta/biosynthesis Mice Neovascularization Non-U.S. Gov't
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0008-5472 1538-7445 1538-7445
DOI:	10.1158/0008-5472.can-03-1489