Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor.
We have previously shown that fibroblast growth factor (FGF)-1-, FGF-4-, or vascular endothelial growth factor (VEGF/VPF)-transfected MCF-7 breast carcinoma cells growing as tumors in nude mice are tamoxifen resistant and/or estrogen independent. These transfectants provide opportunity for study of in situ tumor-induced angiogenesis promoted by the individual angiogenic factors under growth-promoting versus growth-inhibiting hormonal conditions. In the present study, vessels in tumors harvested at varying times after tumor cell injection were immunohistochemically highlighted and vessel morphology and topography were scored on a scale of 0 to 4 by blinded observers. In tumors produced by all cell lines under all growth-promoting hormonal conditions, there was significantly increased abundance (P < 0.05) of edge-associated and intratumor microvessels, but not of stromally located microvessels, when compared with tumor nodules harvested under growth-inhibiting conditions, regardless of the identity of the angiogenic factor or the hormonal treatment. Image analysis of bromodeoxyuridine (BrdU)-labeled nuclei of tumors produced by all cell lines under all hormonal conditions harvested at early time points showed that mean labeling indices were highest for hormonal conditions that produced the most robust growth in that particular cell line, implying that a high BrdU labeling index is a predictor of future tumor growth in individual tumors. These results confirm previous studies that established the importance of neovascularization for tumor growth and provide validation for use of these cell lines to study the process of angiogenesis in vivo. Study of gene expression in endothelial cells in edge-associated or intratumor vessels using this model might reveal mechanisms important in tumor-induced angiogenesis in human breast cancer.
McLeskey
S W
SW
Lombardi Cancer Center, Department of Pharmacology, and School of Nursing, Georgetown University Medical Center, Washington, DC 20007, USA. mcleskes@gunet.georgetown.edu
Tobias
C A
CA
Vezza
P R
PR
Filie
A C
AC
Kern
F G
FG
Hanfelt
J
J
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics; D001973:Bromodeoxyuridine; D002277:Carcinoma / Q000098:blood supply* / Q000235:genetics; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000033:anatomy & histology / Q000187:drug effects; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000503:physiopathology*; D010052:Ovariectomy; D011379:Prognosis; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen; D004958:Estradiol; D005346:Fibroblast Growth Factors; D001973:Bromodeoxyuridine