Tumor Recruitment And Reprogramming ( R & R ) Of Bystander Cells

Tumor recruitment and reprogramming (R&R) of bystander cells in cancer progression. We reported that cancer cells could transform normal host cells in xenograft tumor formation (REF). Using 3-dimensional (3-D) cancer-stromal co-culture and chimeric xenograft tumor formation, we identified that, inside a cancer cell population, there existed a subgroup of metastasis-initiating cells (MICs). Importantly, we found that MICs function as “drivers” to recruit and reprogram dormant cells to become an integral part of the tumor (REF). Bystander cell R&R may be one of the strategies for cancer progression and metastasis. CTCs represent the spreading and metastasizing cancer phenotype and thus represent MICs at metastatic sites. Thus, our proposed work will have important implications in cancer biology (REF). The biomarker and biological behaviors we are able to associate to CTCs will provide confident predictors for cancer progression and clinical response. Several features in cancer-stromal interaction may serve as clues for studying R&R mechanism. First, small nucleotide elements with transformation potential can be packed in exosome vesicles (EVs) of 30-150 nm in size and transmitted between cells (REF). Since we have found that certain CTCs produce large amount of EVs (REF), these exosomes may transmit nucleotide regulatory elements, mostly in the form of non-coding RNAs (ncRNAs) such as microRNA (miRNA), to cause neighboring bystander cell transformation (REF). Second, we