English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic cells with impact on metastasis

MPS-Authors
There are no MPG-Authors in the publication available
External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Prathivadhi-Bhayankaram, S. V., Ning, J., Mimlitz, M., Taylor, C., Gross, E., Nichols, M., et al. (2016). Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic cells with impact on metastasis. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 479(4), 841-846. doi:10.1016/j.bbrc.2016.09.121.


Cite as: https://hdl.handle.net/21.11116/0000-0004-B0B2-B
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. (C) 2016 Elsevier Inc. All rights reserved.