Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

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.

Chalkley Microvessel but not Lymphatic Vessel Density Correlates with Axillary Lymph Node Metastasis in Primary Breast Cancers

“…This finding is consistent with the previous studies (Faoro et al, 2008) indicating although the generation of intratumoral lymphatic vessels may enhance tumor cell metastasis, this may not be an essential requirement as lymphatic spread can occur using pre-existing vessels (Mandriota et al, 2001). Also, there are previous studies showing lymphangiogenesis is not increased in tumor tissues but is even less activated than in normal breast tissue (Boneberg et al, 2009). This phenomenon was explained by that solid tumors do not have lymphatic vessels, due to the increased interstitial pressure created by the proliferating cancer cells (Pepper, 2001).…”

VEGF-C differentially regulates VEGF-A expression in ocular and cancer cells; promotes angiogenesis via RhoA mediated pathway

“…However, the therapeutic efficacies have been found to be modest and transitory followed by restoration of neo-angiogenesis and disease progression. Based on these results, subsequent studies conducted have revealed that the resistance towards anti-VEGF therapies is either due to evasive or pre-existing unresponsiveness [28]. Our observations in this study show evidence that knockdown of VEGF-A lead to enhanced expression of VEGF-C and thus this may compensate for some of the functions of VEGF-A.…”

The Intriguing Role of Bevacizumab in Advanced Breast Cancer – The Search Continues

“…43 In contrast with the enthusiasm for VEGF-targeted growth factor genes -including VEGF -were greater in adjacent normal tissues than in the primary tumour tissue. 44 The authors concluded that primary breast tumours are not a site of active angiogenesis. The role of pro-and anti-angiogenic factors in metastatic tissues needs to be elucidated.…”