Molecular biology of breast cancer metastasis. Molecular expression of vascular markers by aggressive breast cancer cells

Abstract

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies.

Figure 1

(A) Ribonuclease protection assay analysis, (B) differential display analysis, and (C) Northern blot analysis of vascular markers expressed by human breast cancer cell lines, including the following: thrombin receptor, endothelin B receptor (methods described by Kirschmann et al [43]), TIE2, CD31, endoglin and VEGF. Equal loading was assessed by ribosomal protein L32 (L32) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression (A), genes not differentially expressed (B), and β-actin (C). These data are summarized in Table 1.