Shedding light on the effect of radiation therapy on circulating tumor cells

Conference Dates

June 2-6, 2019


Many common treatments for cancer – including radiation therapy (RT) – have the unfortunate side effect of promoting the spread of cancer to other organs [1-3]. While the ‘pro-metastatic’ effects of RT have been known for some time, it has garnered renewed attention in recent years in part due to the widespread study of circulating tumor cells (CTCs). In hematogenous metastasis, CTCs detach from the primary tumor and spread via the blood to other organs and tissues of the body. There are three main hypotheses for RT induced metastasis (RTIM) as reviewed in [1]: i) RT causes disruption of the primary tumor and vasculature, which leads to immediate shedding of CTCs, iii) RT induces biomolecular changes in tumor cells, such as epithelial to mesenchymal transition, leading to increased CTC shedding over time as the tumor cells die, and, iii) Systemic effects, such as the elimination of suppressive signaling molecules by the primary tumor resulting in the proliferation of existent but previously dormant micro-metastases [3].

Our team recently developed a new instrument called ‘Diffuse in vivo Flow Cytometry’ (DiFC; figure 1) [4]. The main advantage of DiFC is that it samples large circulating blood volumes (hundreds of µL per minute), allowing in vivo detection of very rare CTCs. DiFC uses specially designed fiber-optic probe bundles with built-in filters and lenses for efficient collection of weak fluorescent signals and blocking of tissue autofluorescence. As labeled cells pass through the DiFC field of view, transient fluorescent peaks are detected. A custom signal processing algorithm allowed us to determine the number, direction, speed, and depth of circulating cells, and reject false alarm signals from motion artifacts. For example, we recently showed that DiFC allowed detection of early dissemination of green fluorescent protein (GFP)-labeled multiple myeloma cells in a disseminated xenograft model at CTC burdens below 1 cell per mL, as well as rare CTC clusters (fig. 1).

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