In vivo capture and label-free detection of early metastatic cells.
Breast cancer is a leading cause of death for women, with mortality resulting from metastasis. Metastases are often detected once tumour cells affect the function of solid organs, with a high disease burden limiting effective treatment. Here we report a method for the early detection of metastasis using an implanted scaffold to recruit and capture metastatic cells in vivo, which achieves high cell densities and reduces the tumour burden within solid organs 10-fold. Recruitment is associated with infiltration of immune cells, which include Gr1(hi)CD11b(+) cells. We identify metastatic cells in the scaffold through a label-free detection system using inverse spectroscopic optical coherence tomography, which identifies changes to nanoscale tissue architecture associated with the presence of tumour cells. For patients at risk of recurrence, scaffold implantation following completion of primary therapy has the potential to identify metastatic disease at the earliest stage, enabling initiation of therapy while the disease burden is low.
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Samira M
SM
Azarin
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Ji
J
Yi
Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina 29208, USA.
Robert M
RM
Gower
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Brian A
BA
Aguado
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Megan E
ME
Sullivan
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Ashley G
AG
Goodman
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Eric J
EJ
Jiang
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Shreyas S
SS
Rao
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Yinying
Y
Ren
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
Susan L
SL
Tucker
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.|Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, Illinois 60208, USA.|The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611, USA.
Vadim
V
Backman
Department of Surgery, University of Michigan, Ann Arbor, Michigan 48105, USA.|Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611, USA.
Jacqueline S
JS
Jeruss
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA.|Institute for BioNanotechnology in Medicine (IBNAM), Northwestern University, Chicago, Illinois 60611, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48105, USA.|Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48105, USA.
Lonnie D
LD
Shea
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000556:secondary; D000818:Animals; D001672:Biocompatible Materials; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D019736:Prostheses and Implants; D054457:Tissue Scaffolds; D041623:Tomography, Optical Coherence; D047368:Tumor Burden
D001672:Biocompatible Materials