Investigation Of The Role Of Exosomes In Colorectal Cancer Liver Metastasis And The MRI Nano Imaging In Colorectal Inflammation Disease

Colorectal cancer is a common cancer of gastrointestinal tract, whose liver metastasis is the main reason of patient death. But the underlying mechanism remains unclear. Tumor-derived exosomes are emerging mediators of metastasis. Results from studies on melanoma and breast cancer show that exosomes play an important role in cancer metastasis. But whether colorectal cancer-derived exosomes play an important role in colorectal cancer liver metastasis is still unclear.In this study, we demonstrated that exosomes play a pivotal role in colorectal cancer liver metastatic progression. First, a nude mice model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes fromr a highly metastatic colorectal cancer cell (HT-29) can increase the metastatic tumor burden and distribution in target tissue (liver) for colorectal cancer cells with a poor metastatic capacity (Caco-2). We further investigate the mechanism of HT-29-derived exsomes mediated liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes have a relative higher level of CXCR4 in metastatic microenvironment, which indicates that exosomes may affect metastasis by recruiting CXCR4-expressing stromal cells to develop a fit metastatic microenvironment. Finally, migration ability of Caco-2 cells could be increased by tumor-derived exosomes was demonstrated in vitro, which showed another function of exosomes in colorectal cancer liver metastasis progression. This study indicates that the exosomes play important roles in the liver metastasis of colorectal cancer, which offer important implications for the prevention and treatment of colorectal cancer metastasis.Many cancers arise from sites of infection, chronic irritation and inflammation. Solid lipid nanoparticles (SLNs) were synthesized with loading of gadolinium (Gd) diethylenetriaminepenta acetic acid (DTPA) to construct Gd-DTPA-SLNs as an MR T1 contrast agent to evaluate ulcerative colitis. We previously showed that the MR colonography technique enhances inflammatory colorectum based on absorption of nanoparticle contrast agents by colorectal wall, which means that the inflammatory colorectal wall absorb more Gd-DTPA-SLNs.Caco-2 cell monolayers model which simulated the epithelium were applied for the in vitro evaluations of Gd-DTPA-SLN. TNF-α and IL-1β were used to determine the intracellular mechnisms of the inflammatory intestinal epithelial tight junction permeability by using a filtergrown Caco-2 monolayers. Both TNF-α and TNF-α & IL-1β mixture produced a statistically decrease in Caco-2 transepithelial resistance and increased the permeability of Gd-DTPA-SLN obviously. These two inflammatory cytokine damaged tight junction barrier of the monolayers and affected the absorbtion of Gd-DTPA-SLNs in Caco-2 cells. This part of work establishes the "proof-of-principle" of a new imaging technique, called ’nanoparticle-based MR colonography’, which may open new avenues for efficient management of inflammatory bowel disease such as colorectal cancer.In conclusion, our study is mainly focus on colorectal diseases, which showed the roles of exosomes in colorectal cancer liver metastasis and the evaluation of colorectal inflammation with magnetic resonance colonography based on Gd-DTPA-SLN as the contrast agent. This work will provide a new opinion for the diagnosis and treatment of colorectal cancer.