Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling that Coordinates Transendothelial Migration

• DOI: 10.1016/j.celrep.2018.03.092
• Publication Date: 2018-04-17T15:40:31Z
• Authors: Yvona Ward; Ross Lake; Farhoud Faraji; Jamie Sperger; Philip Martin; Cameron Gilliard; Kimberly P. Ku; Tamara Rodems; David Niles; Heather Tillman; JuanJuan Yin; Kent Hunter; Adam G. Sowalsky; Joshua Lang; Kathleen Kelly
• Keywords: Vascular permeability

Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap knowledge concerning platelet-promoted We identify direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is overexpressed antigen several cancer types. Purified extracellular domain or cell-associated stimulated activation. CD97-initiated led granule secretion, including release ATP, mediator endothelial junction disruption. Lysophosphatidic acid (LPA) derived from induced invasiveness via proximal CD97-LPAR heterodimer signaling, coupling coincident cell migration vascular permeability transendothelial migration. Consistent with this, was necessary for cell-induced vivo metastasis formation preclinical models. These findings support targeted blockade as approach ameliorate metastatic spread.