Metastatic disease remains the primary cause of mortality in cancer patients. Yet the number of available in vitro models to study metastasis is limited by challenges in the recapitulation of the metastatic microenvironment in vitro, and by difficulties in maintaining colonized-tissue specificity in the expansion and maintenance of metastatic cells. Here, we show that decellularized scaffolds that retain tissue-specific extracellular-matrix (ECM) components and bound signaling molecules enable, when seeded with colorectal cancer (CRC) cells, the spontaneous formation of three-dimensional cell colonies that histologically, molecularly and phenotypically resemble in vivo metastases. Lung and liver metastases obtained by culturing CRC cells on, respectively, liver and lung decellularized scaffolds retained their tissue-specific tropism when injected in mice. We also found that the engineered metastases contained signet ring cells, which has not previously been observed ex vivo. A culture system with tissue-specific decellularized scaffolds represents a simple and powerful approach for the study of organ-specific cancer metastases.

中文翻译：

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通过在组织特异性脱细胞支架上培养结直肠癌细胞获得的器官特异性转移。

转移性疾病仍然是癌症患者死亡的主要原因。然而，用于研究转移的可用体外模型的数量受到体外转移微环境概括的挑战以及维持转移细胞的扩增和维持中定植组织特异性的困难的限制。在这里，我们显示了保留组织特异性细胞外基质（ECM）成分和结合的信号传导分子的脱细胞支架，当接种结直肠癌（CRC）细胞时，能够在组织学，分子学和表型上自发形成三维细胞集落类似于体内转移。通过分别在以下细胞上培养CRC细胞而获得的肺和肝转移 肝和肺脱细胞支架注入小鼠后，仍保持其组织特异性。我们还发现工程化转移灶中含有印戒细胞，这在体外没有被观察到。具有组织特异性脱细胞支架的培养系统代表了一种简单而强大的方法，用于研究器官特异性癌症转移。