Production of platelet-derived endothelial cell growth factor by normal and transformed human cells in culture.
Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis.
Usuki
K
K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Heldin
N E
NE
Miyazono
K
K
Ishikawa
F
F
Takaku
F
F
Westermark
B
B
Heldin
C H
CH
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016228:Endothelial Growth Factors; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D012867:Skin / Q000378:metabolism; D013552:Swine; D014158:Transcription, Genetic
D016228:Endothelial Growth Factors; D006133:Growth Substances