VEGF and metastasis in breast cancer
Microvessel counts correlate with metastatic disease23
In an analysis of samples from 49 patients with invasive breast cancer, Weidner and colleagues showed that patients whose tumours had a higher MVD were more likely to have metastatic disease.23
Weidner N, Semple JP, Welch WR, Folkman J. N Engl J Med 1991;324:1–8. Copyright © 1991 Massachusetts Medical Society.
In 1991, Judah Folkman, who pioneered research on angiogenesis in cancer, and his group at Harvard Medical School once again made headlines in the New England Journal of Medicine with a report titled ‘Tumour angiogenesis and metastasis - correlation in invasive breast carcinoma.’ In this analysis of primary tumours samples from 49 patients with invasive breast carcinoma (30 with distant or lymph node metastases and 19 without), the authors concluded that microvessel count and density (observed in a microscopic field) were correlated with metastatic disease in axillary lymph nodes or distant sites (or both).23
In a 2005 study, Aldridge et al. showed that VEGF may be involved in breast cancer metastases to bone. Here, staining of bone metastases with antibodies to VEGF (A), CD68 (B) and VEGFR-2 (C) shows localisation of VEGF expression to tumour cells and some bone cells.24
Adapted by permission from Macmillan Publishers Ltd: Br J Cancer 2005;92:1531–7. © 2005.
VEGF and metastases to bone
Expression of VEGF and its receptors by bone metastases24
When breast cancer metastasises, the bones are one of the most common sites of metastasis. Bone metastases of breast cancer tend to be osteolytic. Osteoclasts (bone-resorbing cells that arise from a monocyte/macrophage cell lineage) are thought to be responsible for osteolysis.24
Since monocytes (precursors to osteoclasts) have been shown to express VEGFRs, a relationship between VEGF and breast cancer-derived bone metastases has been hypothesised. In a study of bone metastases from 17 breast cancer patients, Aldridge and colleagues found that VEGF stimulated differentiation of monocytes into osteoclast-like cells capable of resorbing bone. This research suggests that VEGF may be involved in breast cancer metastasis to bone.24
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