Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, 37673, Republic of Korea.
School of Biomedical Convergence Engineering, Pusan National University, Yangsan, Kyungnam, 50612, Republic of Korea.
Adv Sci (Weinh). 2022 Oct;9(29):e2202093. doi: 10.1002/advs.202202093. Epub 2022 Aug 26.
Although metastatic melanoma can be managed with chemotherapy, its heterogeneity and resistance to therapy remain poorly understood. In addition to the spread of melanoma in the bloodstream, melanoma-stroma interaction and the lymphatic system play active roles in said heterogeneity and resistance, leading to its progression and metastasis. Reproducing the complexities of the melanoma microenvironment in vitro will help understanding its progression and enhance the translatability of potential cancer therapeutics. A blood-lymphatic integrated system with heterogeneous melanoma spheroids (BLISH) using the in-bath bioprinting process is developed. The process uniformly prints size-controllable metastatic melanoma spheroids along with biomimetic blood and lymphatic vessels (LVs). The system reproduces hallmark events of metastatic melanoma, such as tumor stroma interaction, melanoma invasion, and intravasation. The application of the system to investigate the anticancer effect of combinational targeted therapy suggests that it can be used to study the pathophysiology of melanoma and improve the accuracy of drug response monitoring in skin cancer.
尽管转移性黑色素瘤可以通过化疗来治疗，但它的异质性和对治疗的耐药性仍未得到很好的理解。除了黑色素瘤在血液中的扩散外，黑色素瘤-基质相互作用和淋巴系统在这种异质性和耐药性中也发挥着积极的作用，导致其进展和转移。在体外重现黑色素瘤微环境的复杂性将有助于了解其进展，并提高潜在癌症治疗药物的转化能力。本研究采用浴内生物打印工艺开发了一种具有异质性黑色素瘤球体的血液-淋巴集成系统（BLISH）。该工艺可以均匀地打印出大小可控的转移性黑色素瘤球体，以及仿生血液和淋巴管（LVs）。该系统再现了转移性黑色素瘤的标志性事件，如肿瘤-基质相互作用、黑色素瘤浸润和血管内渗。该系统在研究组合靶向治疗的抗癌效果中的应用表明，它可用于研究黑色素瘤的病理生理学，并提高皮肤癌药物反应监测的准确性。
