Cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them.[1] Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs),[2] transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings.[1][3] Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms.[4] Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer[5][6] and arthritis.[7] Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.[8][9]
Other organisms[edit]
Eukaryotes[edit]
Plants cells adhere closely to each other and are connected through plasmodesmata, channels that cross the plant cell walls and connect cytoplasms of adjacent plant cells.[27] Molecules that are either nutrients or signals required for growth are transported, either passively or selectively, between plant cells through plasmodesmata.[27]
Protozoans express multiple adhesion molecules with different specificities that bind to carbohydrates located on surfaces of their host cells.[28] cell–cell adhesion is key for pathogenic protozoans to attach en enter their host cells. An example of a pathogenic protozoan is the malarial parasite (Plasmodium falciparum), which uses one adhesion molecule called the circumsporozoite protein to bind to liver cells,[29] and another adhesion molecule called the merozoite surface protein to bind red blood cells.[30]
Pathogenic fungi use adhesion molecules present on its cell wall to attach, either through protein-protein or protein-carbohydrate interactions, to host cells[31] or fibronectins in the extracellular matrix.[32]
Prokaryotes[edit]
Prokaryotes have adhesion molecules on their cell surface termed bacterial adhesins, apart from using its pili (fimbriae) and flagella for cell adhesion.[8] Prokaryotes may have a single or several flagella, either located on one or several places on the cell surface. Pathogenic species such as Escherichia coli and Vibrio cholera possess flagella to facilitate adhesion.[33]
Adhesins can recognise a variety of ligands present on the host cell surfaces and also components in the extracellular matrix. These molecules also control host specificity and regulate tropism (tissue- or cell-specific interactions) through their interaction with their ligands.[34]
Viruses[edit]
Viruses also have adhesion molecules required for viral binding to host cells. For example, influenza virus has a hemagglutinin on its surface that is required for recognition of the sugar sialic acid on host cell surface molecules.[35] HIV has an adhesion molecule termed gp120 that binds to its ligand CD4, which is expressed on lymphocytes.[36] Viruses can also target components of cell junctions to enter host cells, which is what happens when the hepatitis C virus targets occludins and claudins in tight junctions to enter liver cells.[9]
Clinical implications[edit]
Dysfunction of cell adhesion occurs during cancer metastasis. Loss of cell–cell adhesion in metastatic tumour cells allows them to escape their site of origin and spread through the circulatory system.[5] One example of CAMs deregulated in cancer are cadherins, which are inactivated either by genetic mutations or by other oncogenic signalling molecules, allowing cancer cells to migrate and be more invasive.[6] Other CAMs, like selectins and integrins, can facilitate metastasis by mediating cell–cell interactions between migrating metastatic tumour cells in the circulatory system with endothelial cells of other distant tissues.[37] Due to the link between CAMs and cancer metastasis, these molecules could be potential therapeutic targets for cancer treatment.
There are also other human genetic diseases caused by an inability to express specific adhesion molecules. An example is leukocyte adhesion deficiency-I (LAD-I), where expression of the β2 integrin subunit is reduced or lost.[38] This leads to reduced expression of β2 integrin heterodimers, which are required for leukocytes to firmly attach to the endothelial wall at sites of inflammation in order to fight infections.[39] Leukocytes from LAD-I patients are unable to adhere to endothelial cells and patients exhibit serious episodes of infection that can be life-threatening.
An autoimmune disease called pemphigus is also caused by loss of cell adhesion, as it results from autoantibodies targeting a person's own desmosomal cadherins which leads to epidermal cells detaching from each other and causes skin blistering.[40]
Pathogenic microorganisms, including bacteria, viruses and protozoans, have to first adhere to host cells in order to infect and cause diseases. Anti-adhesion therapy can be used to prevent infection by targeting adhesion molecules either on the pathogen or on the host cell.[41] Apart from altering the production of adhesion molecules, competitive inhibitors that bind to adhesion molecules to prevent binding between cells can also be used, acting as anti-adhesive agents.[42]