A variety of tumors contain a small subpopulation of cells, the cancer stem-like cells (CSCs), that play an important role in cancer metastasis. Indeed, these cells multiply indefinitely and are resistant to chemotherapy, radiation therapy, and immunotherapy, playing a critical role in tumor recurrence [1,2]. Thus, research and clinical trials should focus on the evaluation of the treatment on CSCs, but current isolation methods, primarily based on surface markers, have several limitations. It has been demonstrated that altered iron (Fe) metabolism in cancer results in an increase in Fe concentration within tumor cells, and recently, CSCs from a variety of tumor types have been identified as the cells with preferential Fe uptake and storage within a tumor. In this project, we aim to take advantage of the magnetic moment that can be induced in cells with high Fe loadings to separate the CSC population from various subtypes of breast tumors, using in vitro and in vivo testing approaches. We will use several custom-made devices based on permanent magnets, such as the Cell Tracking Velocimetry (CTV) or the Quadrupole Magnetic Sorter (QMS) [3]. Our instruments have the potential to analyze and separate thousands of cells in a few minutes, allowing the quantification of intracellular Fe with resolutions on the order of 10
-15 gr per cell, many orders of magnitude more sensitive on a per-cell basis than any other known instrument. Insight gained from this work will enhance our current understanding of the Fe metabolism and the paramagnetic signature of individual cell types within a bulk tumor as well as a novel means to isolate CSCs from tumors and blood. Thus, this technology could provide the scientific community with a cost-effective, fast, and reliable method to isolate CSCs, which could be used to determine tumor metastasis and to inform the overall efficacy of any novel treatment.
[1] Arnold, C.R.; Mangesius, J.; Skvortsova, I.I.; Ganswindt, U. The Role of Cancer Stem Cells in Radiation Resistance. Frontiers in Oncology 10 (2020) 164.
[2] Dianat-Moghadam, H.; Mahari, A.; Salahlou, R.; Khalili, M.; Azizi, M.; Sadeghzadeh, H. Immune evader cancer stem cells direct the perspective approaches to cancer immunotherapy. Stem Cell Research & Therapy 13 (2022) 150.
[3] Gómez-Pastora, J.; Kim, J.; Weigand, M.; Palmer, A.F.; Yazer, M.; Desai, P.C.; Zborowski, M.; Chalmers, J.J. Potential of Cell Tracking Velocimetry as an Economical and Portable Hematology Analyzer. Scientific Reports 12 (2022) 1-12.
