Dr. Ningling Kang
Tumor Microenvironment and Metastasis
Despite significant advances in the treatment of liver metastatic diseases, liver metastases are still a principle cause for mortality of cancer patients. Dr. Kang’s research program is trying to address the following questions: (1) why is the liver a preferential invasion site for various cancers such as gastrointestinal cancers, melanoma, breast and lung carcinomas? (2) what are key cellular factors within the liver that contribute to the implantation and growth of cancer cells in the liver. The long-term goal of her research is to uncover cellular and molecular mechanisms and identify therapeutic targets within the liver for reducing tumor implantation and metastatic growth in the liver.
The development of liver metastases is dependent on interactions between cancer cells and the liver microenvironment. Cancer cells are the seeds and the liver is like the soil that provides physical support and essential nutrients for seeding of cancer cells. If we could disrupt communications between the seeds (cancer cells) and the soil (the liver), then we would have mechanisms to prevent tumor planting in the liver. Although this “seeds and soil theory” had been developed in 1889, it still remained largely unknown how cancer cells interact with the liver and what the action of the liver microenvironment is. Dr. Kang’s study, which has been funded by NCI K01 and R01 grants, is focused on hepatic stellate cells (HSCs) which are the liver resident pericytes. She and her research team members studied the role of HSCs in tumor growth using primary HSC culture, a HSC/tumor co-implantation mouse model, and experimental liver metastasis mouse models. They also utilized a noninvasive in vivo xenogen imaging technique to detect and quantitate tumor growth in the liver of mice. They found that HSCs were able to activate into tumor associated myofibroblasts to promote tumor growth. Activation of HSC into myofibroblasts was regulated by TGF-beta, a cytokine that is enriched in the liver. When TGF-beta dependent HSC activation process was manipulated by knocking down a protein called IQGAP1, metastatic growth of lung and colorectal cancers in the liver was affected in mice. Their findings were presented on an AACR special conference and published in Journal of Clinical Investigation, 2013.
Dr. Kang had received her research training in the Division of Gastroenterology and Hepatology, Department of Internal Medicine of Mayo Clinic. She collaborated actively with world- renowned scientists at Mayo Clinic Cancer Centers and other research institutes. Her research demonstrating that HSCs are a new therapeutic target for liver metastases would eventually lead to further testing if combinatory therapies that target both cancer cells and the tumor microenvironment could be more effective at reducing liver metastases and increasing the survival benefit of cancer patients.