CaSki cells are a cell line used extensively in biomedical research. A cell line is a population of cells that can be maintained in a laboratory for long periods, providing scientists with a consistent source of human cells for study. Derived from human cervical cancer, CaSki cells are an epithelial cell line, originating from tissue that lines body surfaces. Their primary use is in studying cancer, particularly how viruses contribute to its development.
The Origin and History of CaSki Cells
The CaSki cell line has a well-documented history. These cells were established in 1977 by Dr. R.A. Pattillo and his colleagues from tissue sourced from a 40-year-old female patient diagnosed with epidermoid carcinoma. This type of cancer arises from the flat, scale-like cells that make up the outer surface of the cervix.
A unique aspect of the CaSki cell line’s origin is that the tissue sample was not from the primary tumor in the cervix, but from a metastasis. A metastasis is a secondary cancer growth that has spread from the original site to another part of the body. In this case, the cancerous cells had traveled to and formed a new tumor in the mesentery of the small intestine.
The Link to Human Papillomavirus (HPV)
The most defining feature of CaSki cells is their connection to the Human Papillomavirus (HPV). These cells contain the genetic material of HPV, specifically Human Papillomavirus type 16 (HPV-16). HPV-16 is classified as a “high-risk” type because of its strong association with the development of cervical cancer. The presence of HPV-16 DNA within CaSki cells makes them a useful tool for understanding how the virus drives the transformation of healthy cells into cancerous ones.
The viral DNA in CaSki cells is “integrated,” meaning the virus’s DNA has been inserted directly into the chromosomes of the human host cell. This integration is a primary event in HPV-associated cancer development. Once integrated, the viral genes can be continuously expressed by the cell’s machinery, producing viral proteins that disrupt normal cell functions.
CaSki cells contain a high number of copies of the HPV-16 genome, estimated to be around 600 copies per cell. This high copy number leads to the significant production of two specific viral proteins, known as E6 and E7. These oncoproteins are the primary drivers of cancer, as they interfere with the cell’s natural tumor-suppressing mechanisms, leading to uncontrolled cell growth and preventing the normal process of programmed cell death.
Applications in Scientific Research
The characteristics of CaSki cells make them suitable for a range of research applications centered on HPV and cervical cancer. One area of study is the HPV life cycle itself. Researchers use these cells to investigate how viral genes are expressed and how their proteins function within a host cell.
CaSki cells are frequently used to develop and test new therapies. They serve as a platform for screening potential anti-cancer drugs, where scientists expose the cells to various compounds to see if they can kill the cancer cells or halt their proliferation.
Another application is in immunology and vaccine research. CaSki cells express HPV-16 proteins, which are the targets of therapeutic HPV vaccines. Researchers test whether immune cells, like T-cells stimulated by a vaccine, can recognize and destroy the cancerous cells.
Scientists also use CaSki cells to investigate cellular pathways involved in cancer. By manipulating genes within these cells, researchers can identify the specific cellular machinery that the HPV E6 and E7 proteins interact with.
Key Biological Characteristics
Beyond their viral connection, CaSki cells possess several inherent biological features of interest to researchers. They are an aneuploid cell line, meaning the cells have an abnormal number of chromosomes. This is a realistic feature for modeling the genetic chaos common in tumors, as most cancer cells exhibit aneuploidy.
The cells are of an epithelial type, which is consistent with their origin from the lining of the cervix. This ensures experiments are conducted on the correct type of cell affected by HPV. Their ability to grow adhered to the surface of a culture dish, known as monolayer growth, is characteristic of epithelial cells in a lab setting.
The genetic profile of CaSki cells also shows alterations common to many cancers. For instance, the tumor suppressor gene p53 is wild-type in CaSki cells, though its function is disabled by the HPV E6 protein as previously described. These cells also require a specific nutrient formulation, RPMI-1640 medium, to grow properly in the lab.