Collagen III embedded biomaterial is predicted to decrease collagen network signatures associated with aggressive tumor behavior and suppress tumor progression and metastases at the site of tumor resection.
In cancer patients, mortality results primarily from metastatic disease, and the tumor microenvironment plays a critical role in this process. One component of the tumor stroma that surrounds tumor cells is Collagen III (Col3) and Dr. Volk has discovered that Col3 is a critical regulator of migration and invasion of cancer cells, wherein higher levels of Col3 create a non-permissive tumor micro-environment for cancer metastases.
Dr. Volk’s in vivo genetic studies demonstrated that reduction of Col3 led to increased tumor growth and metastases in a murine breast cancer model, most likely due to increased myofibroblast density and collagen alignment, resulting in a pro-carcinogenic stroma. Conversely, Col3 containing gels significantly inhibited the migration and invasion of human cancer cell lines in vitro. In vivo, reduced levels of Col3 increased breast cancer cell proliferation and diminished apoptosis in a murine model.
Importantly, addition of Col3 to human breast cancer cells injected in a xenograft model increased apoptosis, suggesting that Col3 can directly kill tumor cells. Previous studies in the Volk laboratory show that Col3 is critical for a regenerative healing response. Therefore, Col3 containing biomaterials are expected to successfully limit aggressive behavior (rapid recurrence and metastasis) of cancer cells in vivo following resection while simultaneously promoting healing after surgery.
Dr. Volk is currently collaborating with the Penn School of Engineering to develop and test an implantable biomaterial that replicates a complex Col3 matrix in order to prevent metastatic disease at the site of the primary tumor resection.