A team of investigators has recently discovered that the collagen receptor DDR1 functionally interacts with the insulin-like growth factor system in regulating bladder cancer.
The study entitled “Discoidin Domain Receptor 1 functionally interacts with the IGF-I system in bladder cancer” has been recently accepted in the international-peer-reviewed journal Matrix Biology Plus.
This work is an international collaborative effort between the laboratories of Dr. Andrea Morrione, currently at the Sbarro Institute for Cancer Research and Molecular Medicine, and the Center for Biotechnology at Temple University, Dr. Renato V. Iozzo from the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Dr. Antonino Belfiore from the University of Catania, Italy.
Bladder cancer is one of the most common and aggressive cancers and, regardless of the treatment, often recurs and spread to surrounding tissues. Thus, a better understanding of the mechanisms regulating bladder tumorigenesis is critical for the design and implementation of rational therapeutic strategies.
The authors previously discovered that the membrane protein IGF-IR is critical for the migratory capacity of bladder cancer cells, suggesting a possible role in bladder cancer progression. However, IGF-IR targeting in aggressive bladder cancer cells only partially inhibited growth without attachment of these cells. Significantly, aggressive bladder cancer cells have decreased IGF-IR levels but overexpressed another membrane protein, the insulin receptor isoform A (IR-A), suggesting that the latter may play a more prevalent role than the IGF-IR in bladder tumor progression. The collagen receptor DDR1 functionally cross-talks with both the IGF-IR and IR in breast cancer, and previous data suggest a role of DDR1 in bladder cancer.
The authors discovered that DDR1 is expressed in more aggressive, but not in non-invasive bladder cancer cells. DDR1 is activated upon stimulation with IGF-I, IGF-II, and insulin, interacts with the IGF-IR, and the IR-A and transient DDR1 targeting severely inhibits cell migration. They further demonstrate that DDR1 may link the IGF-IR and IR-A to the regulation of cellular structures critical for the regulation of cancer cell migration. Similarly to the IGF-IR, DDR1 levels are increased in bladder cancer tissues compared to healthy tissue controls.
These findings provide the first characterization of the functional interaction between DDR1 and the IGF-I system and could lead to the identification of novel targets for therapeutic intervention in bladder cancer. Moreover, the expression profiles of IGF-IR, IR-A, DDR1, and downstream effectors could serve as a novel biomarker panel to predict malignancy of bladder cancer.
About the Sbarro Health Research Organization
The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org