May 04, 2016
The College of Pharmacy April Research Publication Highlight showcases the development of a novel three dimensional model of lung cancer to better understand resistance to therapy and identify new strategies in the treatment of lung cancer.
The UK College of Pharmacy Research Publication Highlight for April, 2016 is titled “Investigating the Radioresistant Properties of Lung Cancer Stem Cells in the Context of the Tumor Microenvironment” and was published in Radiation Research.
The project was completed by investigators in the Colleges of Pharmacy and Medicine at the University of Kentucky. Ryan Chan, a graduate student in the Department of Pharmaceutical Sciences in the laboratory of Dr. Meenakshi Upreti, the study’s lead author. Ryan also received the prestigious Scholar-in-Training Award to present this work at the Radiation Research Society Meeting held in Las Vegas, Nevada in 2014. Dr. Ronald McGarry, Department of Radiation Medicine, and postdoctoral scholars from the Upreti lab, Drs. Pallavi Sethi and Amar Jyoti, also contributed to the research.
Sensitivity to chemotherapeutics and radiation therapy has been tested historically in a select number of cancer cell lines. However, these in vitro systems fail to capture the complexity of tumors, which contain multiple cell types that interact with one another and are influenced by factors such as extracellular matrix and a low oxygen microenvironment (hypoxia). The Upreti laboratory has developed a new, multicellular 3D model of the most common form of lung cancer. The 3D co-culture model includes cancer cells, fibroblasts and endothelial cells that develop a complex extracellular matrix and tissue like architecture. These “tumor tissue analogs”, or TTAs, are grown under hypoxic conditions to model the physiological tumor microenvironment. A clever feature of the model is that each cell-type in the TTA is color coded with a fluorescent reporter gene, such that the growth and death of each cell type can be monitored in response to radiation and chemotherapy. TTAs containing cancer stem cells not only failed to respond to radiation treatment, but grew more rapidly. However, when radiation therapy was combined with Cisplatin, a platinum-based chemotherapeutic commonly used in the treatment of lung cancer, the proliferative effect of radiation treatment was attenuated.
“The development of this new model of lung cancer will be useful to reduce false positives in the screening of potential chemotherapeutics and will likely lead to new 3D models for other types of cancer. This research highlights the creativity of the faculty and graduate students at the University of Kentucky” said Greg Graf, Assistant Dean for Translational Research.