PMID- 17692905
OWN - NLM
STAT- MEDLINE
DCOM- 20080520
LR  - 20080305
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 121
IP  - 5
DP  - 2008
TI  - Endothelial capillary tube formation and cell proliferation induced by tumor 
      cells are affected by low molecular weight heparins and unfractionated heparin.
PG  - 637-45
AB  - BACKGROUND: Clinical studies suggest a survival advantage in cancer patients 
      receiving low molecular weight heparin (LMWH). A suggested mechanism for this 
      beneficial effect may reside in the antiangiogenic activity of heparins. 
      OBJECTIVES: In this study we investigated whether two different LMWHs, i.e. 
      enoxaparin and dalteparin, and unfractionated heparin (UFH), affect the 
      angiogenic potential of human microvascular endothelial cells (HMEC-1) promoted 
      by tumor cells. METHODS: HMEC-1 cells were incubated with tumor cell conditioned 
      media (TCM) derived from human breast cancer and leukemic cells (i.e. MCF-7, 
      MDA.MB.231, and NB4 cell lines) or recombinant cytokines (i.e. VEGF, FGF-2, 
      TNF-alpha) +/-heparins. Capillary-like tube formation in Matrigel and cell 
      proliferation were evaluated. RESULTS: All three TCM induced a significant 
      (p<0.05) increase in total length of tubes formed by HMEC-1 in Matrigel. These 
      increases were significantly counteracted (62 to 100% mean inhibition) by 
      enoxaparin and dalteparin, but were significantly less affected by UFH. 
      Similarly, the tube formation induced by standard VEGF, FGF-2, or TNF-alpha was 
      100% inhibited by enoxaparin, and 70-90% by dalteparin, whereas minor or no 
      inhibition was observed with UFH. VEGF was the most active cytokine in TCM of 
      both breast cancer and leukemic cells. EC proliferation was significantly 
      increased by standard angiogenic factors, and slightly affected by breast cancer 
      TCM (p=ns). The addition of heparins significantly counteracted the proliferative 
      stimuli. CONCLUSIONS: These results support a major role for LMWH compared to UFH 
      in inhibiting the proangiogenic effect exerted by tumor cells or purified 
      angiogenic factors on microvascular endothelium.
FAU - Marchetti, Marina
AU  - Marchetti M
AD  - Department of Hematology, Ospedali Riuniti di Bergamo, Largo Barozzi, 1-24128 
      Bergamo, Italy.
FAU - Vignoli, Alfonso
AU  - Vignoli A
FAU - Russo, Laura
AU  - Russo L
FAU - Balducci, Donatella
AU  - Balducci D
FAU - Pagnoncelli, Marcella
AU  - Pagnoncelli M
FAU - Barbui, Tiziano
AU  - Barbui T
FAU - Falanga, Anna
AU  - Falanga A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070810
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Capillaries/*drug effects/physiology
MH  - Cell Proliferation/drug effects
MH  - Endothelial Cells/*drug effects/physiology
MH  - Heparin/*pharmacology
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Neoplasms/blood supply/*drug therapy/pathology
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A/analysis
EDAT- 2007/08/19 09:00
MHDA- 2008/05/21 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/03/13 00:00 [received]
PHST- 2007/06/05 00:00 [revised]
PHST- 2007/06/07 00:00 [accepted]
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/05/21 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - S0049-3848(07)00249-6 [pii]
AID - 10.1016/j.thromres.2007.06.015 [doi]
PST - ppublish
SO  - Thromb Res. 2008;121(5):637-45. doi: 10.1016/j.thromres.2007.06.015. Epub 2007 
      Aug 10.