Angiogenic profile of breast carcinoma determines leukocyte infiltration.
To study the relationship between the angiogenic profile and leukocyte infiltration of tumors, single cell suspensions of archival frozen medullary and ductal breast cancer tissues were analyzed by flow cytometry. The amount of leukocytes and endothelial cells was measured, as well as the expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelial cell fraction. A significantly higher number (3.2-fold) of infiltrating leukocytes was observed in medullary carcinoma. The composition of this infiltrate was similar to that seen in ductal carcinomas. The more intense infiltrate was explained by the approximately 3-fold enhanced endothelial ICAM-1 expression in medullary carcinoma. The angiogenic profile of all tumors was assessed by quantitative real-time reverse transcription-PCR analysis. Vascular endothelial growth factor (VEGF)-C and VEGF-D, but not VEGF-A, basic fibroblast growth factor, placental growth factor, and angiopoietins 1, 2, and 3 showed a relatively higher level of expression in ductal carcinoma than in medullary carcinoma. In vitro, both VEGF-C and VEGF-D were found to decrease endothelial ICAM-1 expression in the presence of basic fibroblast growth factor. These data suggest that in vivo angiogenic stimuli prevent the formation of an effective leukocyte infiltrate in tumors by suppressing endothelial ICAM-1 expression.
Bouma-ter Steege
Jessica C A
JC
Angiogenesis Laboratory, Research Institute for Growth and Development, Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
Baeten
Coen I M
CI
Thijssen
Victor L J L
VL
Satijn
Sietske A
SA
Verhoeven
Inge C L
IC
Hillen
Harry F P
HF
Wagstaff
John
J
Griffioen
Arjan W
AW
D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008207:Lymphatic Metastasis; D009389:Neovascularization, Pathologic; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis
D017931:DNA Primers; D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D017493:Leukocyte Common Antigens