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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Animals

Apoptosis/physiology

Cell Division/physiology

Cell Line; Tumor

Endothelium; Vascular/*metabolism/*pathology

Lymphokines

Melanoma; Experimental/*blood supply/*metabolism/pathology

Mice

Mice; Inbred C57BL

Neovascularization; Pathologic/metabolism/pathology

Platelet-Derived Growth Factor/*biosynthesis

Receptor; Platelet-Derived Growth Factor beta/biosynthesis

Research Support; Non-U.S. Gov't

protease-activated ligand

angiogenesis in-vitro

pdgf-beta-receptor

dermatofibrosarcoma protuberans

factor-b

endothelial-cells

healing wounds

alpha-receptor

inhibition

recruitment

Publication and Content Type

ref (subject category)

art (subject category)