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Radiotherapy and Chemotherapy Promote Metastasis Before Cell Death by Altering Cell Mechanical Properties

A Ekpenyong

N Zetocha , B Lee , S Prathivadhi-Bhayankaram , M Mimlitz , A Ekpenyong*, Creighton University, Omaha, NE


SU-I-GPD-T-639 (Sunday, July 30, 2017) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose: Although radiotherapy and chemotherapy target the proliferation of cancer cells, it is metastasis that leads to over 90% of all cancer deaths. Surprisingly, there is emerging clinical and scientific evidence that certain anti-cancer drugs as well as low dose ionizing radiation can actually promote metastasis, but the mechanisms behind their pro-metastatic effects are not completely known. Here, we seek to determine if the mechanical properties of cells subjected to various cancer drugs and radiotherapy are altered in ways that inadvertently promote metastasis.

Methods: We used a microfluidic microcirculation platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation, to apply in-vivo-like mechanical stimuli on the cells. We also used migration assays and CdSe/ZnS core-shell nanoparticles (quantum dots) to spectroscopically quantify functional changes in cells following chemotherapy and radiotherapy.

Results: We found that leukemic cancer cells treated with doxorubicin and daunorubicin, commonly used anti-cancer drugs, have over 100% longer transit times through the device, compared to untreated leukemic cells. Such delays in the microcirculation are known to promote extravasation of cells, a key step in the metastatic cascade. Furthermore, there was a significant (p < 0.01) increase in the chemotactic migration of the doxorubicin treated leukemic cells. We have extended our microfluidic microcirculation mimetic (MMM) to include the advection of cancer cells irradiated with gamma photons from Co-60 and UV photons.

Conclusion: Both enhanced retention in the microcirculation and enhanced migration following chemotherapy, which we have discovered, are pro-metastatic effects which can serve as new targets for anti-metastatic drugs. For radiotherapy, our results are first steps in evaluating the pro-metastatic effects of low dose irradiation based on their induced alterations in cell mechanical properties, potentially providing a new rationale for the improvement of radiotherapy protocols.

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