The Impacts of Obesity-Associated Alterations in Adipose-Derived Stem Cell on Tumor Development

The tumor microenvironment is composed of various types of cells. Among these cells, mesenchymal stem cells (MSCs) play a critical role in tumor development. Recently, adipose tissue has been found as a rich source of MSCs and the MSCs derived from adipose tissue are termed as adipose-derived stem cells (ADSCs). ADSCs have attracted much recent attention due to their convenient acquisition and regenerative capability and emerged as therapeutic approaches in several medical fields. However, the elusive role of ADSCs in tumor development causes the safety concerns in clinical utilization. On the other hand, obesity is a serious health problem worldwide and associated with incidence of several cancers. Recent reports indicate that obesity accompanies the expansion of ADSCs and changes their biological properties, suggesting that ADSC stimulation may be the alternative mechanism of cancer incidence associated with obesity. Hence, ADSCs are not only an important role in tumor microenvironment but also implied into obesity-related cancer incidence. Previously, we have found that ADSCs promote the tumor initiation and promotion of breast and colon cancer cells. Thus, the long-term objectives of this proposed project are to determine the functional roles of ADSCs in tumor development followed by mechanistic investigation of underlying signaling pathways and to investigate the obesity-related alterations of ADSCs and their impacts on tumor development. A 2-year research project is proposed to accomplish specific aims as follow: Specific aim 1 - Identification of the obesity-induced alterations of ADSCs and their impacts on cancer cells Specific aim 2 - In vivo pre-clinical validation of the tumor-promoting effects of obesity-related ADSCs by non-invasive molecular imaging The completion of this study will not only provide mechanistic explanation of the contribution of ADSC in obesity-related cancer incidence but also suggest a potential therapeutic target in obesity-related cancers.