Grants Funded

Abstract
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but serious potential complication of device-based breast implantation. If caught early, the disease is largely treatable, but severe cases may recur or even lead to death. The exact cause of BIA-ALCL remains unclear, and successful methods of prevention have yet to be developed. The purpose of the present study is to utilize our advanced, three-dimensional in vitro organotypic breast tissue platform for studying the mechanisms underpinning BIA-ALCL. This platform incorporates patient-derived breast tissue which has been processed for cellular components including fat, vascular, glandular, and immunologic cells into a three-dimensional matrix of type 1 collagen, thereby allowing for a high-fidelity recreation of the true breast microenvironment in which cell behavior can be studied. Specifically, a patient-derived line of BIA-ALCL cells will be studied within the platform, and endpoints such as cell growth, invasion, and cell signaling expression will be analyzed both with and without pieces of breast implant incorporated into the platform. The goal of these experiments is to focus on the role played by breast implant materials (both smooth and textured) in the development and progression of BIA-ALCL. In order to achieve this goal, the first aim of the study is to analyze the effect of altered matrix stiffness (via ribosylation or changes in concentration) on BIA-ALCL cell growth and invasion as this property has been shown to significantly affect the behavior of many other types of cancer cells. Next, we will utilize the platform to assess the behavior of the same established BIA-ALCL cell line with no implant, with smooth implant incorporated into the platform, and with textured implant incorporated into the platform. Cell growth and invasion will be assessed in addition to the signaling molecule, IL-6, and its receptor, IL-6R, as this cytokine has been shown in prior studies to be upregulated in clinical cases and in ex vivo models of BIA-ALCL. Such an analysis has the potential to contribute to the etiologic understanding of BIA-ALCL, and it lays the groundwork for future studies of BIA-ALCL within our high-fidelity, high-throughput, three-dimensional organotypic breast tissue platform which may lead to even further understanding of BIA-ALCL pathogenesis in addition to the potential development of ways to avoid this rare but deadly complication of breast implantation.

Biography
Dr. Jason Spector is a nationally recognized clinician, researcher and educator. He holds two patents, and has been an integral part several Cornell University-Weill Cornell Medical College translational research teams. He participates in the NIH and Howard Hughes Medical Institute sponsored Clinical Summer Immersion for Biomedical Engineering Program, mentoring engineering doctoral students. Since 2007, he has been a lecturer at Cornell University's Biomedical Engineering Science and Technology course, "Approaches to Problems in Human Needs." Dr. Spector serves as an Ad-Hoc reviewer for six prestigious medical journals, and has presented at national and international medical meetings. He recently served as Moderator of the Emerging Technologies Section, at the American Surgical Congress in 2011.