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Issue 1, 2014
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Sweeping lymph node micrometastases off their feet: an engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating tumor cells that disseminate to the lymph nodes

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Abstract

Approximately 90% of cancer related deaths are due to metastasis. Cells from the primary tumor can metastasize through either the vascular or lymphatic circulation. Cancer cells in circulation are called circulating tumor cells (CTCs) and it has been shown that bone marrow is a niche for homing of blood borne CTCs from several epithelial tumors. Cancer cells found in bone marrow are termed disseminated tumor cells (DTCs). Likewise, CTCs in the lymphatic circulation are more often seeded in the sentinel lymph nodes (SLN) that drain the tumor. Micrometastases (<2 mm) occur after the arrest and implantation of DTCs in lymph nodes over time. This paper presents a cell culture platform termed microbubbles formed in polydimethylsiloxane (PDMS) from a microfabricated silicon wafer for mimicking lymph node micrometastases. We cultured lymph node seeking cancer cells in microbubbles to evaluate the efficacy of natural killer (NK) mediated therapy for targeting lymph node micrometastasis. The microbubble platform consists of an array of microcavities that provides a unique microenvironment for mimicking the deep cortical unit of the lymph nodes. We show that cancer cells cultured in microbubbles with therapeutic NK cells undergo apoptosis after 24 h in culture. Since lymph node metastases are prevalent across several types of cancer, this platform may be useful for developing improved cancer therapies for targeting lymph node micrometastases.

Graphical abstract: Sweeping lymph node micrometastases off their feet: an engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating tumor cells that disseminate to the lymph nodes

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Publication details

The article was received on 10 May 2013, accepted on 24 Jul 2013 and first published on 25 Jul 2013


Article type: Paper
DOI: 10.1039/C3LC50584G
Citation: Lab Chip, 2014,14, 118-127

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    Sweeping lymph node micrometastases off their feet: an engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating tumor cells that disseminate to the lymph nodes

    S. Chandrasekaran, M. J. McGuire and M. R. King, Lab Chip, 2014, 14, 118
    DOI: 10.1039/C3LC50584G

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