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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

Expression of receptors for angiogenic and lymphangiogenic factors in primary breast cancer. The mRNA expression of angiogenic and lymphangiogenic receptors was quantified by real-time RT-PCR in breast cancer tissues and tumour-adjacent tissues of the same patients. The ratio of the expression in tumour tissue to the respective tumour-adjacent tissue was calculated for each patient. The bars show the mean ratio with s.e.m. for 41 patients. *P<0.05 and ***P<0.001.
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fig3: Expression of receptors for angiogenic and lymphangiogenic factors in primary breast cancer. The mRNA expression of angiogenic and lymphangiogenic receptors was quantified by real-time RT-PCR in breast cancer tissues and tumour-adjacent tissues of the same patients. The ratio of the expression in tumour tissue to the respective tumour-adjacent tissue was calculated for each patient. The bars show the mean ratio with s.e.m. for 41 patients. *P<0.05 and ***P<0.001.

Mentions: For the regulation of angiogenesis, not only the expression of growth factors is important, but also the expression of the respective receptors. Therefore, the mRNA expression of receptors for angiogenic and lymphangiogenic factors was analysed by quantitative real-time RT-PCR and the ratio of the expression in a breast cancer sample to the expression in the tumour-adjacent tissue of the same patient was calculated (Figure 3). The VEGF receptors were downregulated in breast cancer tissues compared to the respective tumour-adjacent tissues: the mean VEGF-R1 (FLT1) expression in the tumour tissue was reduced to 47%, VEGF-R2 (KDR) to 49% and VEGF-R3 (LT4) to 49% of the expression levels in tumour-adjacent tissues. For neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2), which can act as enhancers for VEGF-R signalling, we found a mean decrease of NRP-1 in breast tumour tissue to 55% of the expression levels in tumour-adjacent tissues, whereas NRP-2 expression showed no significant difference between tumour and tumour-adjacent tissues. The angiopoietin receptor TIE-2 was reduced to 40% in breast cancer tissues compared to tumour-adjacent tissues. For the two PDGF receptors, PDGF-Rα and PDGF-Rβ, the mean expression in breast cancer samples was reduced to 41 and 72% of the expression levels found in tumour-adjacent tissues. CXCR2, the receptor for angiogenic chemokines, was reduced in the breast cancer tissues to 56% of the level in the-adjacent tissues, whereas CXCR3, the receptor for angiostatic chemokines, was upregulated 3.4-fold.


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)

Expression of receptors for angiogenic and lymphangiogenic factors in primary breast cancer. The mRNA expression of angiogenic and lymphangiogenic receptors was quantified by real-time RT-PCR in breast cancer tissues and tumour-adjacent tissues of the same patients. The ratio of the expression in tumour tissue to the respective tumour-adjacent tissue was calculated for each patient. The bars show the mean ratio with s.e.m. for 41 patients. *P<0.05 and ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Expression of receptors for angiogenic and lymphangiogenic factors in primary breast cancer. The mRNA expression of angiogenic and lymphangiogenic receptors was quantified by real-time RT-PCR in breast cancer tissues and tumour-adjacent tissues of the same patients. The ratio of the expression in tumour tissue to the respective tumour-adjacent tissue was calculated for each patient. The bars show the mean ratio with s.e.m. for 41 patients. *P<0.05 and ***P<0.001.
Mentions: For the regulation of angiogenesis, not only the expression of growth factors is important, but also the expression of the respective receptors. Therefore, the mRNA expression of receptors for angiogenic and lymphangiogenic factors was analysed by quantitative real-time RT-PCR and the ratio of the expression in a breast cancer sample to the expression in the tumour-adjacent tissue of the same patient was calculated (Figure 3). The VEGF receptors were downregulated in breast cancer tissues compared to the respective tumour-adjacent tissues: the mean VEGF-R1 (FLT1) expression in the tumour tissue was reduced to 47%, VEGF-R2 (KDR) to 49% and VEGF-R3 (LT4) to 49% of the expression levels in tumour-adjacent tissues. For neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2), which can act as enhancers for VEGF-R signalling, we found a mean decrease of NRP-1 in breast tumour tissue to 55% of the expression levels in tumour-adjacent tissues, whereas NRP-2 expression showed no significant difference between tumour and tumour-adjacent tissues. The angiopoietin receptor TIE-2 was reduced to 40% in breast cancer tissues compared to tumour-adjacent tissues. For the two PDGF receptors, PDGF-Rα and PDGF-Rβ, the mean expression in breast cancer samples was reduced to 41 and 72% of the expression levels found in tumour-adjacent tissues. CXCR2, the receptor for angiogenic chemokines, was reduced in the breast cancer tissues to 56% of the level in the-adjacent tissues, whereas CXCR3, the receptor for angiostatic chemokines, was upregulated 3.4-fold.

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