Function of Maximal Microvessel Density in Breast Tumor Metastasis

摘要

Abundant data implicates maximal microvessel density in breast and many other solid tumors as being a strong prognostic indicator. These data are gained by quantitating the number of microvessels in 'hot spots' of high-density tumor vasculature, implying that such hot spots have functional significance in the process of metastasis. We proposed that gene expression in the area of the microvascular hot spots is different from elsewhere in the tumor and that genes upregulated in these areas may be functioning to promote metastasis. We have produced experimental tumors in mice and harvested them so as to preserve spatial relationships within the tumor. Microvessel densities were quantitated in several areas of each tumor. Pulmonary metastases were also quantitated and correlated with the maximal microvessel density for each tumor. Areas of tumor adjacent to the microvascular hot spots in the most metastatic tumors were microdissected along with similar sized spots not associated with hot spots. RNA was extracted from these microdissected samples and used to synthesize cDNA. Microarray analysis will be used to discover genes differentially expressed in areas adjacent to hot spots compared with areas not associated with hot spots.