PMID- 7707422
OWN - NLM
STAT- MEDLINE
DCOM- 19950509
LR  - 20190512
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 87
IP  - 4
DP  - 1995 Feb 15
TI  - Inhibition of development of murine melanoma lung metastases by systemic 
      administration of recombinant platelet factor 4.
PG  - 304-9
AB  - BACKGROUND: When administered locally, recombinant platelet factor 4 (rPF4), a 
      known angiogenesis inhibitor, has been shown to effectively suppress murine 
      melanoma and human colon carcinoma primary tumor growth in mice. It was 
      tentatively concluded that this effect was due to the inhibition of tumor 
      neovascularization. PURPOSE: This study has evaluated the effects of systemically 
      administered rPF4 on the growth and establishment of experimental B16F10 melanoma 
      lung metastases in syngeneic mice. METHODS: B16F10 cells (0.5-1.0 x 10(5) were 
      administered intravenously to mice; 21 days later, the lungs were removed and the 
      tumor foci were counted. Treatments with rPF4 were given to C57BL/6J mice 
      immediately following tumor inoculation either (a) intravenously as a single dose 
      (0.375, 0.75, 1.5, or 2.0 mg) or as multiple doses (6 mg total) over a 48-hour 
      period, (b) subcutaneously or intramuscularly as multiple doses (6 mg total) over 
      a 72-hour period, or (c) subcutaneously as multiple doses (6 mg total) over a 92- 
      or 96-hour period following a delay of 4, 24, or 48 hours. (BALB/cByJ x 
      C57BL/6)F1 (CByB6F1/J) athymic nude mice received rPF4 subcutaneously over a 
      72-hour period. The ability of rPF4 to block binding of 51Cr-labeled B16F10 tumor 
      cells to matrix-coated microtiter plates was evaluated in vitro. The in vivo 
      effect of intravenously injected rPF4 on the retention of 51Cr-labeled B16F10 
      cells was examined by determining the remaining lung-associated radioactivity 
      after 30 minutes or 1, 2, or 4 hours. RESULTS: Intravenous administration of rPF4 
      significantly inhibited the development of metastatic lung nodules in a 
      dose-dependent fashion as assessed by both lesion number (P < .03) and lung 
      weight (P < .05). When initiation of subcutaneous treatment with rPF4 was delayed 
      24-48 hours, the number of metastatic foci was significantly reduced (P < .05). 
      The antitumor effect of rPF4 was not dependent on a T-lymphocyte-mediated 
      process, since subcutaneous rPF4 treatment also suppressed the number of lung 
      metastases in T-cell-deficient athymic CByB6F1/J nude mice. In vitro experiments 
      demonstrated modest inhibitory effects (28%) of rPF4 on B16F10 tumor cell binding 
      to purified murine vitronectin. However, lung clearance experiments at early time 
      points (0.5 hour and 1 hour) showed that tumor lodging was not affected by rPF4 
      treatment. CONCLUSIONS: The administration of rPF4 by systemic routes inhibited 
      the development of experimental lung metastases. These findings are consistent 
      with the known angiostatic properties of rPF4, and we conclude that inhibition of 
      metastatic tumor formation may be due to inhibition of tumor-induced 
      neovascularization. IMPLICATIONS: These results support the testing of rPF4 as an 
      angiostatic agent in the treatment of metastatic tumors.
FAU - Kolber, D L
AU  - Kolber DL
FAU - Knisely, T L
AU  - Knisely TL
FAU - Maione, T E
AU  - Maione TE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Recombinant Proteins)
RN  - 37270-94-3 (Platelet Factor 4)
SB  - IM
MH  - Animals
MH  - Cell Adhesion
MH  - Disease Models, Animal
MH  - Female
MH  - Injections, Intramuscular
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Lung Neoplasms/*drug therapy/physiopathology/secondary
MH  - Melanoma/*drug therapy/physiopathology/secondary
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Platelet Factor 4/administration & dosage/*therapeutic use
MH  - Recombinant Proteins/administration & dosage/therapeutic use
EDAT- 1995/02/15 00:00
MHDA- 1995/02/15 00:01
CRDT- 1995/02/15 00:00
PHST- 1995/02/15 00:00 [pubmed]
PHST- 1995/02/15 00:01 [medline]
PHST- 1995/02/15 00:00 [entrez]
AID - 10.1093/jnci/87.4.304 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1995 Feb 15;87(4):304-9. doi: 10.1093/jnci/87.4.304.