Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer.
BACKGROUND
Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer.


METHODS
We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women.


RESULTS
We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers.


CONCLUSIONS
Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours.
Boneberg
E-M
EM
Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland.
Legler
D F
DF
Hoefer
M M
MM
Ohlschlegel
C
C
Steininger
H
H
Füzesi
L
L
Beer
G M
GM
Dupont-Lampert
V
V
Otto
F
F
Senn
H-J
HJ
Fürstenberger
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger