DF/HCC Program Affiliation

Angiogenesis, Invasion and Metastasis

Research Abstract

The Moses Lab has had a long-standing interest in identifying and characterizing the biochemical and molecular mechanisms underlying the regulation of angiogenesis during tumor progression, from the angiogenic switch through metastasis. Dr. Moses and her group have discovered five different angiogenesis inhibitors, three of which are in clinical development for use against a variety of cancers.

Significant efforts are now underway in the lab to identify the genes and proteins that they encode, that are responsible for the ''angiogenic switch''. This critical checkpoint, during which time a tiny benign, avascular tumor acquires the vascular phenotype, is a prerequisite for subsequent tumor growth and progression. The Moses Lab has recently identified and validated a number of genes which are differentially expressed during the angiogenic switch and is currently developing molecular and biochemical interventions to prevent the switch from occurring by targeting some of these genes.

In addition, the Moses Lab has, as part of their long term Urinary Proteomics Initiative, developed a number of sensitive and specific non-invasive urine tests for different cancers. These cancer tests are based on the lab's work focused on the detection of biomarker proteins purified from the urine of cancer patients. A number of these urine tests are currently in clinical testing as potential cancer diagnostics and prognostics.

Publications

• Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA.ADAM 12 cleaves ECM proteins: Correlation with cancer status and stage.J Biol Chem 2004 Sep 20.
  15381692
• Fernández CA, Butterfield C, Jackson G, Moses MA.Structural and functional uncoupling of the enzymatic and angiogenic inhibitory activities of tissue inhibitor of metalloproteinase-2 (TIMP-2): loop 6 is a novel angiogenesis inhibitor.J Biol Chem 2003 Oct
  12900406
• Yan L, Borregaard N, Kjeldsen L, Moses MA.The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL.J Biol Chem
  11486009
• Fang J, Shing Y, Wiederschain D, Yan L, Butterfield C, Jackson G, Harper J, Tamvakopoulos G, Moses MA.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model.Proc Natl Acad Sci U S A 2000 Apr 11;97(8):3884-9.
  10760260