Department of Biomedical Engineering, Cornell University, Weill Hall, Ithaca, NY 14853, USA.
Lab Chip. 2014 Jan 7;14(1):118-27. doi: 10.1039/c3lc50584g.
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.
大约 90%的癌症相关死亡是由于转移。原发肿瘤的细胞可以通过血管或淋巴循环转移。循环中的癌细胞称为循环肿瘤细胞（CTCs），已经表明骨髓是来自几种上皮肿瘤的血源性 CTC 归巢的龛位。骨髓中发现的癌细胞称为播散性肿瘤细胞（DTCs）。同样，淋巴循环中的 CTCs 更容易在引流肿瘤的前哨淋巴结（SLN）中定植。随着时间的推移，DTC 在淋巴结中的停滞和植入导致微转移（<2 毫米）的发生。本文提出了一种细胞培养平台，称为从微加工硅片上的聚二甲基硅氧烷（PDMS）中形成的微泡，用于模拟淋巴结微转移。我们将具有淋巴结趋向性的癌细胞培养在微泡中，以评估自然杀伤（NK）介导的疗法靶向淋巴结微转移的疗效。微泡平台由微腔阵列组成，为模拟淋巴结深部皮质单位提供了独特的微环境。我们表明，在培养 24 小时后，与治疗性 NK 细胞共培养的微泡中的癌细胞发生凋亡。由于淋巴结转移在几种类型的癌症中很常见，因此该平台可能有助于开发针对淋巴结微转移的改进癌症疗法。
