Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases

Sep 1, 2017Cancer research

Bone-driven production of a cell receptor helps target nanotherapy to breast cancer spread

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Abstract

Integrin β3 was significantly elevated on bone metastases in 42 breast cancer patients compared to primary tumors.

  • Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries.
  • In a preclinical model, integrin β3 was strongly expressed on bone metastatic cancer cells but not on primary mammary tumors or visceral metastases.
  • Mechanistic investigations indicated that TGFβ signaling through SMAD2/SMAD3 is necessary for the induction of β3 in breast cancer within the bone.
  • A micelle-based nanoparticle therapy targeting integrin αvβ3 demonstrated specific localization to breast cancer bone metastases in mice.
  • Using this targeted delivery system for docetaxel, bone tumor burden was significantly reduced with less bone destruction and reduced hepatotoxicity compared to free docetaxel.
  • Mice treated with the nanoparticle-encapsulated docetaxel showed a significant decrease in tumor cell proliferation within the bone compared to those treated with free docetaxel.

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