Abstract 3589: The use of a novel orthotopic xenograft model of fusion negative rhabdomyosarcoma to study the effect of ASAP1 on tumor progression and metastasis

Abstract

Abstract ASAP1 is a multidomain ADP-ribosylation factor (Arf) GTPase-activating protein (GAP) involved in the regulation of the actin cytoskeleton, focal adhesions dynamics and receptor tyrosine kinases trafficking. ASAP1 expression levels correlate with progression of solid tumors (e.g. breast, colorectal, pancreatic, ovarian, gastric, and prostate cancer). The first evidence for a role of ASAP1 in cancer progression was the discovery that the amplification of ASAP1 gene on chromosome 8 correlates with poor prognosis in uveal melanoma. A similar amplification of chromosome 8 has been reported in ~72% of fusion negative rhabdomyosarcoma (FN-RMS) tumors, suggesting a potential role for ASAP1 signaling in the progression of FN-RMS. To determine the function of ASAP1 in tumor growth, invasion and metastasis, we used a tongue orthotopic xenograft of FN-RMS which recapitulates physiologically relevant tumor progression and metastasis to lymph nodes and lungs, two of the common metastatic sites in patients. Using intravital microscopy, we observed that injected FN-RMS cells formed elongated structures and exhibited dynamic branching, which might represent local invasion. H&E stained of fixed tissue revealed invasion into the tongue and local metastasis. Metastases to the regional lymph nodes, lower mandible and lungs were also observed. Using this system, we are now able to determine effect of knocking down and knocking out ASAP1 on the progression of the xenografts, including invasion in real time and metastasis. Citation Format: Sarah M. Hammoudeh, Yeap Ng, Mukesh P. Yadav, Roberto Weigert, Paul A. Randazzo. The use of a novel orthotopic xenograft model of fusion negative rhabdomyosarcoma to study the effect of ASAP1 on tumor progression and metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3589.