Recombinant platelet factor 4, an angiogenic marker for human breast carcinoma.
The present study was designed to test the hypothesis that rhPF4 binds with high specificity to the neovasculature of breast cancer carcinoma. To achieve this goal, we used intravital microscopy to study the binding characteristics of systemically injected fluorescently labeled rhPF4 (FITC-rhPF4) to the microvasculature of dorsal skinfold chambers in nude mice implanted with tumor spheroids prepared from the human breast cancer cell line MCF-7. Our results show that intravenously as well as intra-arterially injected FITC-rhPF4 exclusively labeled, with high intensity and specificity, the endothelium of the breast cancer induced neovasculature. Only on rare occasions (0.7 +/- 1.5 site per cm2 skinfold), short (37 +/- 48 microns) intense labeled sites were found in the normal vasculature of the skinfold. Heparin could displace most of the label if injected within 10 min after the rhPF4-injection, but not 30 min after. In conclusion, our results show that rhPF4 preferentially binds to regions of active angiogenesis in vivo, supporting the concept of using rhPF4 conjugates to target tumors in cancer patients. Certain rhPF4 conjugates could have applications as imaging agents, with potential utility in identification, screening, detection, prognosis or staging of breast cancer and other cancers. Other similar conjugates, bearing therapeutic isotopes or toxins might be useful in selective treatment strategies.
Borgström
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Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
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D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010978:Platelet Factor 4 / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D012867:Skin / Q000098:blood supply; D014183:Transplantation, Heterologous
D011994:Recombinant Proteins; D010978:Platelet Factor 4; D016650:Fluorescein-5-isothiocyanate