Breast cancer increases initiation of angiogenesis without accelerating neovessel growth rate.
BACKGROUND
Recurrence and mortality rates in patients with breast cancer correlate with the degree of tumor angiogenesis (angiogenic index). We have developed a novel angiogenesis model by using disks of fresh human placental vein that initiate an angiogenic response and exhibit linear radial capillary growth in culture. We hypothesized that the addition of human breast cancer cells to this human placental vein angiogenesis model would increase the incidence of angiogenesis and accelerate the rate of neovessel growth compared with vein disk cultured without tumor cells.


METHODS
To test this hypothesis, vein explants from seven human placentas were incorporated into clots of 0.3% fibrin in Medium 199 and fetal bovine serum with or without 1.5 x 10(5) T-47D (n = 6 placentas) or MCF-7 (n = 1 placenta) breast cancer cells. Statistical differences between the experimental (with breast cancer cells) and control (no added cells) cultures were determined by repeated measures ANOVA.


RESULTS
The proportion of disks exhibiting neovessel growth (initiation) by day 12 was significantly increased in the presence of T-47D cells (p < 0.05 at day 12, p < 0.001 at day 15). No statistical difference was seen in rates of neovessel growth (millimeters per day). Similar results were seen with MCF-7 cells.


CONCLUSIONS
Tumor enhancement of angiogenesis may occur by increased initiation of the angiogenic response. Subsequent vessel growth rates may be tumor independent. We predict that effective antiangiogenic therapies will block a tumor's ability to augment angiogenesis initiation rather than subsequent neovessel growth.
Watson
J C
JC
Department of Surgery, Louisiana State University Medical Center, New Orleans 70112, USA.
Redmann
J G
JG
Meyers
M O
MO
Alperin-Lea
R C
RC
Gebhardt
B M
BM
Delcarpio
J B
JB
Woltering
E A
EA
D000704:Analysis of Variance; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D002196:Capillaries / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D009389:Neovascularization, Pathologic; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D014407:Tumor Cells, Cultured; D014680:Veins / Q000166:cytology* / Q000473:pathology
D003470:Culture Media