Bioengineering Department, University of Texas at Arlington, Arlington, TX 76019-0138, USA.
Biomaterials. 2012 Jan;33(3):876-85. doi: 10.1016/j.biomaterials.2011.10.002. Epub 2011 Oct 22.
Inflammatory responses and associated products have been implicated in cancer metastasis. However, the relationship between these two processes is uncertain due to the lack of a suitable model. Taking advantage of localized and controllable inflammatory responses induced by biomaterial implantation and the capability of tissue scaffolds to release a wide variety of chemokines, we report a novel system for studying the molecular mechanisms of inflammation-mediated cancer metastasis. The animal model is comprised of an initial subcutaneous implantation of biomaterial microspheres which prompt localized inflammatory responses, followed by the transplantation of metastatic cancer cells into the peritoneal cavity or blood circulation. Histological results demonstrated that substantial numbers of B16F10 cells were recruited to the site nearby biomaterial implants. There was a strong correlation between the degree of biomaterial-mediated inflammatory responses and number of recruited cancer cells. Inflammation-mediated cancer cell migration was inhibited by small molecule inhibitors of CXCR4 but not by neutralizing antibody against CCL21. Using chemokine-releasing scaffolds, further studies were carried out to explore the possibility of enhancing cancer cell recruitment. Interestingly, erythropoietin (EPO) releasing scaffolds, but not stromal cell-derived factor-1α-releasing scaffolds, were found to accumulate substantially more melanoma cells than controls. Rather unexpectedly, perhaps by indirectly reducing circulating cancer cells, mice implanted with EPO-releasing scaffolds had ~30% longer life span than other groups. These results suggest that chemokine-releasing scaffolds may potentially function as implantable cancer traps and serve as powerful tools for studying cancer distraction and even selective annihilation of circulating metastatic cancer cells.
炎症反应及其相关产物与癌症转移有关。然而，由于缺乏合适的模型，这两个过程之间的关系尚不确定。我们利用生物材料植入诱导的局部和可控炎症反应以及组织支架释放各种趋化因子的能力，报告了一种研究炎症介导的癌症转移分子机制的新系统。该动物模型由生物材料微球的初始皮下植入组成，这会引发局部炎症反应，随后将转移性癌细胞移植到腹腔或血液循环中。组织学结果表明，大量 B16F10 细胞被招募到生物材料植入物附近的部位。生物材料介导的炎症反应的程度与招募的癌细胞数量之间存在很强的相关性。趋化因子释放支架进一步研究了抑制炎症介导的癌细胞迁移的可能性。有趣的是，与基质细胞衍生因子-1α释放支架相比，发现释放促红细胞生成素（EPO）的支架会积聚更多的黑素瘤细胞。也许出人意料的是，通过间接减少循环中的癌细胞，植入 EPO 释放支架的小鼠的寿命比其他组延长了约 30%。这些结果表明，趋化因子释放支架可能潜在地作为可植入的癌症陷阱，并作为研究癌症转移和甚至选择性消除循环转移性癌细胞的有力工具。
