The Differential Expression of Chemokines and Chemokine Receptors in Mesenchymal Stem Cells Tumor Tropism

• Main Authors: Yu-Hsiu Lai, 賴育秀
• Other Authors: 鄭旭辰
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/89562846720929842182

碩士 === 國立中興大學 === 生命科學院碩士在職專班 === 98 === Mesenchymal stem cells (MSCs) are non-haematopoietic stromal cells with the ability to proliferate and differentiate into mesenchymal tissues such as bone, cartilage and adipose. Several studies indicate that systemically infused MSCs can migrate into damaged or diseased tissues, and have a lot of clinical beneficial effects. On the other hand, MSCs also have been shown to be recruited by endocrine and paracrine signals released from the tumor site. But the mechanisms underlying these phenomena remain unclear. In this study, we used in vivo imaging system (IVIS) to investigate MSCs tumor tropism in animal model. MSCs modified to express firefly luciferase were systemically injected into tumor-bearing animals (4T1 and CT26) and their non-tumor bearing counterparts. In vivo experiments showed that MSCs selectively homing to 4T1 tumor site, but not CT26 tumor-bearing site. Previous studies have indicated that MSCs are known to functionally express chemokine receptors, which might be responsible for their tumor-homing process. Therefore, we hypothesized that 4T1 may secreted a variety of chemokines to attract MSCs. To evaluate the differential expression of genes between 4T1 and CT26, the total RNA were extracted from 4T1 tumor and CT26 tumor, respectively. Subsequently, microarray analysis containing over 41,000 transcripts were performed. The differential expressed genes were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expressions of some chemokines (CCL24, CXCL1, CXCL2, CXCL7 and VEGF-C) were up-regulated in 4T1-bearing tumor. qRT-PCR was also used to examine the expression of CCR3 (receptor for CCL24), CXCR2 (receptor for CXCL1, CXCL2 and CXCL7) and VEGFR3 (receptor for VEGF-C) in MSCs. These results indicated that MSCs could homing to a specific type of tumor but not all tumors. Furthermore, CCL24, CXCL1, CXCL2, CXCL7 and VEGF-C seem to be involved in the MSCs tumor homing. To explore the role of chemokine receptors in MSCs tumor-specific homing, specific knockout or overexpression of chemokine receptors in MSCs will pursue further.