Microfluidics: a powerful tool for producing a three-dimensional invasive tumor model

Microfluidics: a powerful tool for producing a three-dimensional invasive tumor model
Parisa Poornemat,^1,* Zeinab bagheri,²
1. Faculty of Life Sciences and Biotechnology, Shahid Beheshti University , Tehran, Iran
2. Faculty of Life Sciences and Biotechnology, Shahid Beheshti University , Tehran, Iran
Introduction: Invasive behaviors of cancer cells such as metastasis, angiogenesis, migration, and integration of cancer cells together are key factors in cancer mortality. These behaviors lead to the progression of cancer cells and make treatment more difficult. They can change the type and dose of the drug needed to treat cancer cells or affect the way the drug works, failing conventional therapies, increased mortality, and treatment costs. Therefore, identifying different aspects of these behaviors is very important in designing new drugs, choosing the right drug dose, drug delivery, and ultimately successful cancer treatment [2]. standard methods for evaluating cancer cells and testing drugs are animal models and two-dimensional cell culture. Animal models had limitations such as high cost and complete incompatibility with in vivo conditions [1,2]. Despite its advantages, such as reasonable cost and availability, two-dimensional cell culture, has the disadvantage of not mimicking cell-to-cell and cell-to-extracellular matrix interactions. In addition, growth signals are not available. As a result, three-dimensional cell culture systems are proposed that are very successful and reliable in pharmacological studies and understanding of cancer cells and can mimic cell interactions, provide uniform growth conditions for all cells, and distribute the environment evenly. 3D cell culture models are divided into two categories: liquid base and scaffold base [3]. Scaffold bases are obtained from synthetic or natural polymers and provide cell growth and extracellular matrix. 3D cell culture includes methods such as rotary cell culture, plate culture system, hanging drop culture method, and magnetic levitation method that can be used to create cells [4]. A Scaffold's independent model is spheroid tumors, which are self-assembling and capable of growing from single-celled suspensions. They also have morphological and physiological characteristics similar to cancer cells [4].
Methods: One of the most popular platforms for Assessment invasive behaviors is microfluidic chips. Microfluidic chips allow the control of nanoscale and microscale fluids and provide the conditions for biological processes that were very difficult to perform in the current cell culture model. The design of chips used to study the invasive behavior should allow observation of behaviors such as cell migration and metastasis. For example, Yan et al developed a microfluidic device to study the migration of cancer cells to different organs. Their platform containing a porous polycarbonate membrane in the center, surrounded by two layers of PDMS containing a central well and five wells around them. For testing the chip, the cell suspension was poured into the central hole, then FBS and media were added to the system from under the membrane to evaluate migration [12].
Results: Truong et al. designed a microfluidic chip to evaluate cells' morphological changes and proliferation when exposed to the EGF gradient. They found that when cells are cultured with CAFs, their invasive behavior increases [11]. In another study, Xiaohui et al designed a microfluidic droplet chip to study the angiogenesis of HUVEC cells. This system allows the secretion of VEGF, which stimulates angiogenesis. They found that the process of angiogenesis was stopped in the presence of the anticancer drug Fingolimod [10]. Also, Kong et al. designed a microfluidic system to measure the potential of different types of lung cancer cells for metastasis. The results showed that the potential for metastasis in lung, bone marrow, and liver cells was far greater than muscle cells. [7,8].
Conclusion: Recent developments show that microfluidic chips are a suitable platform for evaluating cancer cells' invasive behavior, affecting the treatment and effectiveness of drugs and leading to the death of patients.
Keywords: microfluidic chips, 3D cell culture, spheroid, cancer, invasive behavior.