The human body relies on a complex network of cells, each performing specialized tasks to maintain health. Proteins on cell surfaces often act as communicators, influencing how cells interact and behave. CD99 is one such protein, widely distributed and involved in various cellular processes. Understanding CD99 provides insights into fundamental biology and its implications for human health.
Understanding CD99
CD99, also known as Cluster of Differentiation 99, is a cell surface glycoprotein. It is a protein with attached sugar molecules on the outer membrane of cells. CD99 is encoded by the MIC2 gene, found on the pseudoautosomal regions of both the X and Y chromosomes. It exists in two main forms, a long (Type I) and a short (Type II) isoform, generated through alternative splicing, leading to differing functions.
While expressed at low levels in nearly all human cell types, CD99 is particularly abundant on certain immune cells. These include immature thymic T-lineage cells, tonsillar lymphoid progenitor cells, and other hematopoietic cells. Its presence on these cells highlights its role in immune system development and function. The protein has a mass of approximately 32 kilodaltons (kD).
Diverse Functions of CD99
CD99 plays a role in several biological processes. It is involved in cell adhesion, where cells stick to each other and their surroundings. This adhesion is important for maintaining tissue structure and enabling cell-to-cell communication. CD99 acts as an adhesion molecule, influencing interactions between immune cells and other cell types.
The protein also participates in cell migration and cell signaling. CD99 influences the movement of various immune cells, including leukocytes, monocytes, and neutrophils, across endothelial barriers, a process known as transendothelial migration. This movement is important for immune responses and inflammation. In T cells, CD99 contributes to cell proliferation, activation, and differentiation. It is also involved in the transport of proteins, including Major Histocompatibility Complex (MHC) class I molecules, to the cell surface.
CD99 in Disease and Diagnostics
CD99 is an important marker in the diagnosis of certain diseases, particularly cancers. It is recognized for its strong expression in Ewing’s Sarcoma (EWS), an aggressive pediatric bone tumor. Pathologists routinely use immunohistochemistry to detect CD99, helping distinguish EWS from other similar small round cell tumors. Its consistent presence in EWS makes it a reliable diagnostic tool.
Beyond diagnosis, CD99 also plays a role in EWS biology. High CD99 expression in EWS cells contributes to their aggressive characteristics, including cell migration and invasion. Research indicates that targeting CD99 in EWS cells can reduce tumor growth and induce cell death. This suggests CD99 could be a promising therapeutic target for this cancer.
CD99’s involvement extends to other conditions, where its role can vary. It is highly expressed in several types of leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and in the stem cells of myelodysplastic syndromes (MDS). In these instances, CD99 is associated with disease-initiating stem cells and may contribute to their proliferation and treatment resistance. Conversely, in some cancers like Hodgkin’s lymphoma, osteosarcoma, and gastric cancer, low CD99 expression might be associated with tumor progression. This dual role highlights the complex nature of CD99’s function in disease, and continued research may lead to new diagnostic methods and therapeutic strategies.