Korea University: Development of Microfluidic Chio Capable of Verifying Drug Resistance of Cancer Cells Through In Vitro Culture

Professor Seok Chung’s group of the Department of Mechanical Engineering in the College of Engineering conducted a joint study with Dr. Hyunho Kim of the Harvard Medical School, Professor Jason K. Sa of the College of Medicine at KU and Professor Hye Won Lee of the National Cancer Center. They developed a microfluidic chip capable of verifying the resistance of cancer cells to anti-cancer drugs by culturing a patient’s cancer cells with their adjacent cells. Dr. Hyunho Kim is now taking a postdoctoral course at the Harvard Medical School, and Professor Hakho Lee of the Harvard Medical School also participated in the present study. The research results were published online in Advanced Science (IF: 16.8), a globally renowned journal, on June 3.

Providing patient-customized treatment requires the selection of drugs appropriate to the genomic information of the patient’s cancer cells, the characteristics of those cancer cells, and the environment of the cancer tissue. However, due to the genetic diversity of tumors, genomic information alone can barely provide suitable targeted therapies. In addition, animal tests performed using mice often fail to represent diverse human cells and tumor microenvironments. Overcoming these limitations necessitates using human cells to reconstruct the features of the original tumor environment in which the cancer cells grow.

In the present study, microfluidic chip technology was employed to allow the cancer cells separated from a cancer patient to grow in their specific microenvironment. The microfluidic chip developed in this study was particularly targeted to metastatic lung cancer cells located in the brain because the uniqueness of the brain often prevents the conventionally administered drugs from functioning. Unique features of the brain microenvironment, such as the blood brain barrier or astrocytes, form a mechanism that protects cancer cells.

The research team reconstructed the brain microenvironment by culturing a microenvironment consisting of cerebrovascular cells, astrocytes and extracellular matrix in a microfluidic chip. In addition, the team successfully performed a coculture with cancer cells derived from a patient with brain metastatic lung cancer. The drug response of a cancer cell culture only and the drug response of a co-culture with the microenvironment was compared using genome sequencing and molecular profiling. The comparison revealed the changes in the lung cancer cells caused by the brain microenvironment.

Compared with the existing cell culture platform, the microfluidic chip has a short intercellular interval of micrometers allowing the concentrations of cytokines (or chemical factors) secreted from cells to rapidly increase and be maintained in the channel, thereby realizing close-knit intercellular signal transmission. In this way, the microfluidic chip can recapitulate a process in which cancer cells and microenvironmental cells are assimilated with each other as in vivo.

The anticancer drugs used in clinical settings were applied to the chips, and the results showed that the drug responses differed from the genomic predictions. When the lung cancer cells were cultured in the brain microenvironment, the cancer cell survival rate increased and the transcriptional network profile changed. This process may approximate the drug resistance factors formed in the bodies of actual patients.

The research team commented, “We developed a nonclinical study platform that can reconstruct the interaction between cancer cells and their surrounding microenvironment. This interaction plays the principal role in contributing to the resistance against existing cancer therapies. This platform will be used to investigate the molecular biological mechanisms of the cancer cell-paracancerous microenvironment ecosystem and prepare new anticancer treatment strategies.”

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