Mouse anti Human ICAM1 monoclonal antibody, clone 25D22

Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte-colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumoradjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma (PPARG) visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling-the major signaling receptor for collagen-as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between PPARG visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelialto-mesenchymal transition-as in fibrosis and metastasisand genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandinendoperoxide synthase 2 (PTGS2) colorectal tumor expression is associated with a fibrotic signature in adipose-tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high PTGS2 expression in colorectal tumors is significantly associated with higher concentrations of serum amyloidAand glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose-tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted.

Background: Prostate cancer (PCa) is the second leading cause of cancer-related deaths worldwide. Prostate-specific G-protein-coupled receptor (PSGR) has been identified as a new potential biomarker and therapeutic target for PCa. However, the influence of exosomal PSGR on PCa metastasis remains unknown. This study aimed to identify the regulatory role of exosomal PSGR in the bone microenvironment, prior to metastasis of PCa and the underlying mechanism. Methods: hFOB1.19 cells were co-cultured with PC-3 exosomes exhibiting PSGR overexpression. Alkaline phosphatase (ALP) and von Kossa staining methods were used to measure the osteogenesis of hFOB1.19 cells. RNA sequencing was used to screen the downstream target genes of PSGR and the signaling pathways involved. The expression of the candidate genes was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Results: ALP and von Kossa staining results showed that PC-3 exosomes with overexpressed PSGR enhanced osteogenesis of hFOB1.19 cells. A total of 853 mRNAs were differentially expressed in hFOB1.19 cells of the PSGR-overexpressing PC3 cell (PC3PSGR+ exosome) group compared to the negative exosome control (NC) group, among which 182 mRNAs were significantly upregulated and 671 were downregulated. The functional enrichment and pathway analysis showed that differentially expressed mRNAs were mainly involved in cellular responses to interleukin-1 (IL1), chemotaxis, inflammation, transcriptional misregulation in cancer, and MAKP and NF-kappa B signaling pathways. qRT-PCR showed that levels of intercellular adhesion molecule-1 (ICAM1), RELB proto-oncogene, NF-kappa B subunit (RELB), and IL1 beta (IL1B) were significantly decreased in hFOB1.19 cells of the PSGR-overexpression group. Conclusions: This study suggests that PSGR may regulate the MAKP and NF-kappa B signaling pathways involved in the process of bony metastases by targeting ICAM1, RELB, and IL1B.