Functional Characterization of TPF (Tumor Promoting Factor), A Novel Angiogenic Factor in Breast Cancer Pathogenesis
Annual rept. 1 Jun 2000-31 May 2004
DUKE UNIV MEDICAL CENTER DURHAM NC
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The later stages of human cancer development are poorly understood complex processes associated with the expression of genes by cancers that promote specific tumorigenic activities, such as angiogenesis and metastasis. In the present study, we identified periostin whose acquired expression by human cancers leads to a significant enhancement in tumor angiogenesis and metastasis. Undetectable in normal human breast tissues, periostin was found to be overexpressed by human primary breast cancers examined. Tumor cell lines engineered to overexpress periostin showed accelerated angiogenesis and metastasis as xenografts in immune-compromised animals. The underlying mechanism of angiogenesis was found to derive in part from the up-regulation of the VEGF receptor Flk-1KDR by endothelial cells through an integrin alphavbeta3-FAK mediated signaling pathway. These findings demonstrate the presence of a novel mechanism by which tumor angiogenesis is acquired with the expression of periostin as a crucial step in later stages of tumorigenesis.
- Anatomy and Physiology
- Medicine and Medical Research