Cancer cell culture involves growing cancer cells outside the body under carefully controlled laboratory conditions. This technique provides scientists with a reproducible system to investigate the fundamental biological processes that drive tumor growth and spread. By isolating and maintaining these cells in vitro (in glass), researchers can probe the mechanisms of malignancy and evaluate new therapeutic agents without risk to a living organism. This ability to manipulate and study cancer cells is a foundational element of modern oncology research, allowing for rapid experiments that translate into advancements in patient treatment.
What is Cancer Cell Culture
Cancer cell culture provides a controlled environment for studying cancer progression and treatment sensitivity. Researchers utilize two main sources of cells: primary cell lines and established cell lines. Primary cells are isolated directly from a patient’s tumor tissue and closely maintain the genetic characteristics of the original tumor, but only for a limited number of passages.
Established cell lines, such as the widely used HeLa cells, have acquired the ability to proliferate indefinitely. These immortalized lines are easy to grow, store, and share, making them suitable for large-scale experimental work. However, their long culture history can lead to accumulated genetic alterations, causing them to deviate from the characteristics of a tumor inside the body. The choice depends on the specific research question, balancing physiological accuracy against the requirements for high-throughput screening.
Standard Methods of Growing Cells
Maintaining a healthy cancer cell culture requires creating an artificial environment that mimics the temperature and nutrient supply of the human body. Cells are grown in a specialized plastic vessel submerged in a culture medium, which serves as their food source. This medium is a complex liquid containing salts, amino acids, vitamins, and growth factors, often supplemented with animal serum.
The vessel is placed inside an incubator that precisely regulates the environment, maintaining 37°C and a carbon dioxide (CO2) level of about 5%. This CO2 concentration regulates the pH of the culture medium, ensuring optimal chemical conditions for growth. To prevent contamination, all handling must be performed using strict aseptic technique within a sterile hood.
As cells multiply, they eventually cover the surface of the vessel, a state known as confluence, which slows their growth. To prevent overcrowding, subculturing or passaging is necessary. This involves using an enzyme, like trypsin, to detach the cells, diluting the suspension, and transferring a portion to a new vessel. This routine division allows the cell population to be expanded and ensures the continuous maintenance of the cell line.
Different Types of Cancer Models
Historically, cancer cells were grown as two-dimensional (2D) monolayers, adhering to a flat plastic surface. While simple and cost-effective for initial studies, this method has limitations because cells lose the natural three-dimensional structure and cell-to-cell signaling present in a real tumor. The artificial 2D environment can also alter a cell’s gene expression, affecting its response to drugs.
To overcome these limitations, researchers developed three-dimensional (3D) cell culture models that better replicate tumor architecture. One model is the spheroid, a simple, spherical aggregate of cancer cells that self-assembles without a scaffold. Spheroids offer improved physiological relevance by creating natural gradients of oxygen and nutrients, resulting in layers of cells with differing growth rates, similar to a solid tumor.
A more advanced 3D model is the organoid, a miniature, self-organized structure derived from stem cells or patient tumor cells. Cancer organoids, or tumoroids, are cultured within a supportive material that mimics the extracellular matrix. They are valuable for modeling the tumor microenvironment, including cell signaling and drug transport.
Key Applications in Cancer Research
The use of cancer cell culture models directly impacts the development of new treatments and the understanding of disease progression. A widespread application is high-throughput drug screening, where researchers rapidly test thousands of chemical compounds against cultured cancer cells. Established cell lines are highly amenable to this process due to their ease of production, allowing for the quick identification of promising therapeutic candidates.
Cell culture is also transforming personalized medicine. Patient-derived organoids (PDOs) can be grown from a patient’s own tumor biopsy, creating a unique biological model of their specific cancer. Scientists can then test various drugs on the PDO to predict which treatment will be most effective for that patient before administering it in the clinic.
Cell culture provides a controlled platform for studying the mechanisms of cancer metastasis, the process by which cancer cells spread to distant sites. By culturing cells with other cell types, such as immune or stromal cells, researchers investigate cell-to-cell interactions and the influence of the tumor microenvironment. These models allow for the dissection of specific molecular steps involved in cancer dissemination, which is essential for developing therapies that stop the disease from spreading.