CD271 is a protein located on the surface of various cells throughout the human body. This protein is also known by alternative names, including Nerve Growth Factor Receptor (NGFR) and p75 neurotrophin receptor (p75NTR). It is classified as a type I transmembrane protein, typically weighing approximately 75 kilodaltons. The presence of CD271 has been observed on a diverse range of cell types, such as neurons, Schwann cells, mesenchymal stem/stromal cells, and melanocytes.
The Dual Function of CD271
CD271 exhibits a complex and seemingly contradictory role in cellular signaling, capable of promoting both cell survival and programmed cell death, known as apoptosis. This paradoxical behavior is largely determined by the specific protein partners with which CD271 interacts on the cell surface.
When CD271 forms a complex with receptor tyrosine kinases, specifically Trk receptors such as TrkA, and binds to neurotrophins like Nerve Growth Factor (NGF), it typically enhances the pro-survival signaling pathways initiated by Trk receptors. This partnership can activate downstream cascades, including the NFκB pathway, which contributes to cell growth and survival. Conversely, CD271 can trigger apoptosis under different circumstances. This occurs when it binds to immature forms of neurotrophins, such as pro-NGF or pro-BDNF, particularly when it forms a complex with sortilin. This interaction can activate cell death pathways involving JNK and subsequently, caspases, through adaptor proteins like TRAF6.
Role in the Nervous System
The dual signaling capabilities of CD271 play an important role in the development and maintenance of the nervous system. During early neural development, CD271 helps guide the growth of neurons and refine the intricate connections they form. Its balanced signaling ensures the proper formation of neural circuits.
In the context of nerve injury, CD271’s actions become particularly relevant, influencing whether damaged neurons survive or undergo cell death. Its pro-survival pathways can support neuronal recovery and regeneration after injury. However, its pro-apoptotic pathways can contribute to the loss of neurons, potentially hindering functional restoration. Imbalances in CD271 signaling are also implicated in neurodegenerative conditions, where its pro-death signals may contribute to the progressive loss of neurons observed in these diseases.
A Marker for Stem Cells
CD271 serves as a valuable surface marker for identifying and isolating specific populations of mesenchymal stem cells (MSCs), which are adult stromal cells found in various tissues. MSCs possess the capacity to differentiate into multiple cell types, including bone, cartilage, and fat cells, and exhibit immunomodulatory properties. They are considered promising for regenerative medicine applications.
Scientists use CD271 to purify a particularly potent subset of MSCs, especially from sources like bone marrow and adipose tissue. CD271-positive MSCs from these tissues generally show higher rates of proliferation and greater potential for differentiation into osteogenic, chondrogenic, and adipogenic lineages compared to cells lacking CD271 expression. This characteristic allows for the isolation of more therapeutically effective cells for research and potential use in tissue repair therapies, such as promoting bone healing or cartilage regeneration. While CD271 is a useful marker for uncultured MSCs, its expression can decrease when these cells are expanded extensively in laboratory cultures.
Connection to Cancer
CD271 has gained considerable attention in oncology due to its association with cancer stem cells (CSCs). CSCs are a small, resilient subpopulation of cells within tumors that are believed to drive tumor growth, enable metastasis, and contribute to resistance against conventional cancer therapies. These cells possess self-renewal capabilities and can generate the diverse cell types found in a tumor mass.
CD271 has been identified as a marker on CSCs in several aggressive cancers. In melanoma, for instance, CD271 marks tumor-initiating cells and is linked to increased tumorigenicity, metastatic behavior, and drug resistance. High levels of CD271 in melanoma can promote a shift in cell behavior from a highly proliferative state to a more invasive one. The protein is also found on CSCs in other cancers, including pancreatic cancer and certain types of breast cancer. The presence of CD271 on CSCs is often associated with a poorer clinical prognosis for patients. However, this also presents a potential opportunity for developing new cancer therapies specifically designed to target and eliminate these treatment-resistant CSCs.