Targeting Integrin for the Intervention of Tumor Growth and Metastasis

Background: Understanding how tumors co-opt vasculature to promote tumor growth and spread is aiding the development of new clinical therapeutics for cancer. Angiogenesis and lymphangiogenesis play key roles in controlling the spread of tumors. The molecular processes mediating each of these processes are complex. A central process involves integrins and how they influence blood and lymphatic vessel growth by promoting endothelial cell migration and survival. Integrins play a role in how myeloid progenitor cells, originating from the bone marrow, migrate to the site of inflammation to promote angiogenesis and lymphangiogenesis. Integrins play a central role in vasculogenesis, the process of de novo blood vessel formation. Integrins represent potential targets for pharmacological agents and offer new treatment opportunities to control malignant metastases. In turn, integrins are regulated by phosphoinositide 3-kinases (PI3Ks). PI3Ks represent a family of dual specificity kinases that regulate numerous biological processes, including cell growth, proliferation, and migration.

Technology Description: Researchers at UC San Diego have investigated the effect of PI3kinase inhibition on a key integrin (integrin-alpha4beta1) to block tumor inflammation, angiogenesis, growth, and metastasis. This technology relates to the discovery of the convergence of diverse receptors and signaling pathways on the activation of integrin-alpha4beta1. Phosphoinositide 3-kinase inhibitors can significantly inhibit the clustering and activation of the alpha4beta1 integrin on the myeloid cells, reducing tumor inflammation and growth and ultimately reducing metastatic spread of the malignancy.

The inventors have demonstrated, using a specific PI3kinase inhibitor, blockage of myeloid cell adhesion to endothelium in vitro. Further experiments in mouse models of implanted and spontaneous cancer shows that myeloid cell invasion of tumors is hindered, with subsequent suppression of tumor growth and metastasis. These gamma isoform inhibitors of this technology are relatively non-toxic when compared to pan-isoform PI3kinase inhibitors.

Intellectual Property Information: A provisional patent application has been filed and this invention is available for licensing.

Related Materials:

  • Schmid MC, Varner JA. 2009 Circulating endothelial progenitor cells. Methods Mol Biol. 2009;467:139-55.
  • Garmy-Susini B, Varner JA. (2008) Roles of integrins in tumor angiogenesis and lymphangiogenesis. Lymphat Res Biol. 6(3-4):155-63.
  • Published international patent application on related technology (2007/092471).

Case Number: SD2009-201

Inquiries To: invent@ucsd.edu