Organoids as Complex In Vitro Models for Studying Radiation-Induced Cell Recruitment
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Cellular and Molecular Bioengineering ( 2020) https://doi.org/10.1007/s12195-020-00625-0
Review
Organoids as Complex In Vitro Models for Studying Radiation-Induced Cell Recruitment BENJAMIN C. HACKER1 and MARJAN RAFAT
1,2,3
1
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; 2Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; and 3Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA (Received 16 January 2020; accepted 10 June 2020) Associate Editor Michael R. King oversaw the review of this article.
Abstract—Patients with triple negative breast cancer (TNBC) typically receive chemotherapy, surgery, and radiation therapy. Although this treatment improves prognosis for most patients, some patients continue to experience recurrence within 5 years. Preclinical studies have shown that immune cell infiltration at the irradiated site may play a significant role in tumor cell recruitment; however, little is known about the mechanisms that govern this process. This lack of knowledge highlights the need to evaluate radiation-induced cell infiltration with models that have controllable variables and maintain biological integrity. Mammary organoids are multicellular three-dimensional (3D) in vitro models, and they have been used to examine many aspects of mammary development and tumorigenesis. Organoids are also emerging as a powerful tool to investigate normal tissue radiation damage. In this review, we evaluate recent advances in mammary organoid technology, consider the advantages of using organoids to study radiation response, and discuss future directions for the applications of this technique. Keywords—Cell–cell interactions, triple negative breast cancer, ionizing radiation, radiotherapy, immune cell co-culture, organoid models, recurrence.
INTRODUCTION Breast cancer is the most commonly diagnosed form of cancer and the second most lethal in American women.116 Unchecked tumor cell growth occurs as a result of dysfunctional regulation of proliferation within terminal mammary ducts. Histologically, most breast cancers emerge as ductal carcinoma in situ (DCIS), where cancer cells are still contained within Address correspondence to Marjan Rafat, Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA. Electronic mail: [email protected]
the basement membrane surrounding the lobular units. Once cancer cells have escaped the basement membrane, the disease progresses to invasive ductal carcinoma (IDC), where cells can metastasize to other organs through the vasculature or lymphatic system.141 Breast cancer is a heterogeneous disease, but it is phenotypically classified by the presence of three receptors: estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2). For patients with cancer overexpressing one or more of these receptors, treatments have been developed to target the overexpressed markers. However, for patients
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