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Author Prathivadhi-Bhayankaram, Sruti V. ♦ Ning, Jianhao ♦ Mimlitz, Michael ♦ Taylor, Carolyn ♦ Gross, Erin ♦ Nichols, Michael ♦ Guck, Jochen ♦ Ekpenyong, Andrew E.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANIMAL TISSUES ♦ CHEMOTHERAPY ♦ DOXORUBICIN ♦ IN VIVO ♦ MECHANICS ♦ METASTASES ♦ MIGRATION ♦ NEOPLASMS
Abstract Although most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis therapy. Surprisingly, emerging evidence suggests that certain anti-cancer drugs such as paclitaxel and doxorubicin can actually promote metastasis, but the mechanism(s) behind their pro-metastatic effects are still unclear. Here, we use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation, to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show 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, we report a significant (p < 0.01) increase in the chemotactic migration of the doxorubicin treated leukemic cells. Both enhanced retention in the microcirculation and enhanced migration following chemotherapy, are pro-metastatic effects which can serve as new targets for anti-metastatic drugs. - Highlights: • Doxorubicin enhances migration of leukemic cancer cells before cell death. • Doxorubicin and Daunorubicin stiffen and delay cells in mimicked microcirculation. • Some cancer drugs cause changes in cell mechanics that lead to pro-metastatic effects. • Cell mechanics becomes a new target for anti-metastatic drugs.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-10-28
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 479
Issue Number 4


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