Endocrine Abstracts

Background: Adrenocortical carcinoma (ACC) is the most common type of adrenal cancer. Although only 7% of ACC cases have bone metastasis, these patients have a poor prognosis and reduced quality of life due to severe skeletal related events. Establishing bone metastatic models that allow for the study of tumor progression and therapeutic regimen testing is an important translational research tool for clinical benefit.

Objectives: Specifically, during this symposium we would like to receive feedback from the ACC research community on the applicability and relevance of our approach to ACC.

Methods: Expand our clinically relevant models of bone metastases that encompass intravital multiphoton microscopy (iMPM), engineered bone window systems, in vitro bone mimetic environments, and spatial analysis of patient-derived tissues, to study ACC progression and response to therapy in bone.

Results: We generated in vivo models of cancer in bone based on intra-tibia injection of luciferase expressing cell lines or patient-derived xenografts (PDX) suitable to test the response to chemotherapy, radiation and anti-angiogenic therapy. Growth kinetics were followed, along with survival monitoring, and endpoint immunofluorescence analysis performed on select markers. We further created a tissue-engineered bone construct (TEBC) that, after directimplantation of cancer cells, is combined with an adjacent skin window, allowing for non-destructive intravital examination of tumor growth. iMPM displays both sensitivity and time-resolution to identify dynamic interactions between cancer cells and bone 3D adaptive niches, which support therapy response and resistance. To flank these in vivo dynamic analyses, we established a pipeline for ex vivo extraction of topological information related to the molecular and cellular niches involved in tumor progression and response to treatment in both mouse and human samples. In addition, we generated ex vivo bone mimetic environments to propagate PDXs and patient-derived cells in a bone-like environment and tested therapy response.

Discussion/Conclusion: The tuneability of our bone metastatic models make them an attractive platform for studying ACC bone metastasis.