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Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer.

Boneberg EM, Legler DF, Hoefer MM, Ohlschlegel C, Steininger H, Füzesi L, Beer GM, Dupont-Lampert V, Otto F, Senn HJ, Fürstenberger G - Br. J. Cancer (2009)

Bottom Line: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis.We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated.This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland.

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Quantification of angiogenic and antiangiogenic growth factors in serum. The concentration of angiogenic and antiangiogenic factors were determined by ELISA in the sera of breast cancer patients at the time of diagnosis and the sera of healthy controls. The horizontal line indicates the median of each group. ***P<0.001.
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fig5: Quantification of angiogenic and antiangiogenic growth factors in serum. The concentration of angiogenic and antiangiogenic factors were determined by ELISA in the sera of breast cancer patients at the time of diagnosis and the sera of healthy controls. The horizontal line indicates the median of each group. ***P<0.001.

Mentions: The levels of angiogenic factors in blood have been considered as surrogate markers for tumour angiogenesis. We therefore analysed the concentration of several angiogenesis-regulating factors in the sera of 35 breast cancer patients at the time of diagnosis and compared them to serum levels found in 72 healthy women. ANG-1, HGF and PDGF-AB were found in significant lower levels in the sera of breast cancer patients than in healthy controls (Figure 5). VEGF-A was present in similar amounts in the sera of patients and controls. However, endostatin, a potent angiostatic factor, was significantly increased (1.4-fold) in the sera of breast cancer patients. This increase has been described before (Kuroi et al, 2001) and further corroborates the finding that the production of antiangiogenic factors is elevated in breast tumours. The concentrations of ANG-2 and FGF-2 were below the detection limits of the respective ELISAs. Our real-time RT-PCR data demonstrate that breast tumours do not produce increased amounts of angiogenic factors. In accordance to these data, we found no elevated levels of these factors in the sera of patients. Taken together, these findings indicate that primary breast tumours are not a significant source of angiogenic growth factors. In contrast, the tumours release angiostatic factors as endostatin. These tumour-derived angiostatic molecules could be responsible for the systemic downregulation of angiogenic factors as ANG-1, HGF or PDGF-AB, which were decreased in the sera of breast cancer patients.


Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer.

Boneberg EM, Legler DF, Hoefer MM, Ohlschlegel C, Steininger H, Füzesi L, Beer GM, Dupont-Lampert V, Otto F, Senn HJ, Fürstenberger G - Br. J. Cancer (2009)

Quantification of angiogenic and antiangiogenic growth factors in serum. The concentration of angiogenic and antiangiogenic factors were determined by ELISA in the sera of breast cancer patients at the time of diagnosis and the sera of healthy controls. The horizontal line indicates the median of each group. ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2736814&req=5

fig5: Quantification of angiogenic and antiangiogenic growth factors in serum. The concentration of angiogenic and antiangiogenic factors were determined by ELISA in the sera of breast cancer patients at the time of diagnosis and the sera of healthy controls. The horizontal line indicates the median of each group. ***P<0.001.
Mentions: The levels of angiogenic factors in blood have been considered as surrogate markers for tumour angiogenesis. We therefore analysed the concentration of several angiogenesis-regulating factors in the sera of 35 breast cancer patients at the time of diagnosis and compared them to serum levels found in 72 healthy women. ANG-1, HGF and PDGF-AB were found in significant lower levels in the sera of breast cancer patients than in healthy controls (Figure 5). VEGF-A was present in similar amounts in the sera of patients and controls. However, endostatin, a potent angiostatic factor, was significantly increased (1.4-fold) in the sera of breast cancer patients. This increase has been described before (Kuroi et al, 2001) and further corroborates the finding that the production of antiangiogenic factors is elevated in breast tumours. The concentrations of ANG-2 and FGF-2 were below the detection limits of the respective ELISAs. Our real-time RT-PCR data demonstrate that breast tumours do not produce increased amounts of angiogenic factors. In accordance to these data, we found no elevated levels of these factors in the sera of patients. Taken together, these findings indicate that primary breast tumours are not a significant source of angiogenic growth factors. In contrast, the tumours release angiostatic factors as endostatin. These tumour-derived angiostatic molecules could be responsible for the systemic downregulation of angiogenic factors as ANG-1, HGF or PDGF-AB, which were decreased in the sera of breast cancer patients.

Bottom Line: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis.We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated.This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, Switzerland.

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus