Mouse Anti-FZD2 Recombinant Antibody (clone 9G6) (CAT#: MOB-2608z)

Wang, Ying, et al. "Tumor-contacted neutrophils promote metastasis by a CD90-TIMP-1 juxtacrine-paracrine loop." Clinical Cancer Research 25.6 (2019): 1957-1969. https://doi.org/10.1158/1078-0432.CCR-18-2544

This research investigates the prognostic significance of tumor-infiltrating neutrophils (TINs) in breast cancer, specifically comparing their impact in different tissue compartments. The study evaluated CD66b+ neutrophils in 341 breast cancer samples across multiple cohorts and demonstrated that neutrophils in tumor parenchyma, rather than those in stroma, serve as an independent poor prognostic factor. Mechanistically, the researchers uncovered a CD90-TIMP-1 juxtacrine-paracrine loop between tumor cells and neutrophils. Tumor-contacted neutrophils secrete TIMP-1, which induces epithelial-mesenchymal transition (EMT) in breast cancer cells. In turn, breast cancer cells undergoing EMT enhance neutrophils' TIMP-1 secretion through CD90 in a cell-contact dependent manner. This bidirectional interaction promotes metastasis, and blocking either TIMP-1 or CD90 significantly reduced metastasis in mouse models.
Creative Biolabs provided the neutralizing antibodies against Frizzled2 (CAT#: MOB-2608z-S(P)) that were used in the mixed coculture system to investigate how cancer cells undergoing EMT induce TIMP-1 overexpression in neutrophils. These antibodies helped the researchers identify the specific membrane proteins involved in the cell-contact dependent signaling between cancer cells and neutrophils, revealing CD90 as the key mediator. This contribution was crucial for elucidating the juxtacrine-paracrine loop mechanism and establishing potential therapeutic targets that could disrupt the metastasis-promoting interaction between neutrophils and breast cancer cells.