Project description:We performed global microRNA expression profiling of a cohort of primary melanoma patient samples linked to a well-annotated clinical database. The goal of this study was to identify microRNA that are associated to or correlated with various clinical parameters and patient outcomes. Candidate microRNA were identified for building prognostic models and functional testing. 92 primary melanoma (well-annotated with long clinical follow-up) and 9 congenital nevi samples were analyzed to Exiqon miRCURY two color arrays. The reference sample used was an equal combination of all samples analyzed. By this design, ratio data of test sample/reference is mean-centered data.
Project description:We performed global microRNA expression profiling of a cohort of primary melanoma patient samples linked to a well-annotated clinical database. The goal of this study was to identify microRNA that are associated to or correlated with various clinical parameters and patient outcomes. Candidate microRNA were identified for building prognostic models and functional testing. 119 primary melanoma samples were analyzed in two color arrays. The reference sample used was an equal combination of all samples analyzed. By this design, ratio data of test sample/reference is mean-centered data.
Project description:Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor-stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.