Abstract
Breast cancer is a leading cause of death for women, with mortality resulting from metastasis. Metastases are often detected once tumor 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 tumor burden within solid organs 10-fold. Recruitment is associated with infiltration of immune cells, which include Gr1hiCD11b+ 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 tumor 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.
Highlights
Breast cancer is a leading cause of death for women, with mortality resulting from metastasis
circulating tumour cells (CTCs) can remain in the circulation for long periods of time before homing to and colonizing a metastatic site, with some tumour cells being shed at early points during tumour progression[5,6]
We develop a biomaterial implant to recruit and capture metastatic cells, combined with an imaging system using inverse spectroscopic optical coherence tomography (ISOCT) for label-free detection of cancer cells at the implant, that together constitute a system to detect early metastases
Summary
Breast cancer is a leading cause of death for women, with mortality resulting from metastasis. Modulation of the local immune environment may be a versatile approach for recruiting tumour cells that is distinct from strategies that mimic the microenvironment of a target organ, such as bone[17,18] To this end, the immune response at the implant, which consists of numerous cell types such as macrophages and neutrophils, is hypothesized to mediate recruitment of tumour cells[8,10,12,16,19,20], and this mechanism of recruitment is investigated through localized delivery of the chemokine CCL22 and transplantation of myeloid-derived suppressor cells. Recruited tumour-associated myeloid-derived suppressor cells, in part, contribute to the formation a pre-metastatic niche, which supports a permissive environment for the capture of tumour cells in the scaffold This approach for immune cell-mediated capture and early detection of metastatic cells has the potential to be broadly applicable to many types of cancer
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