(A) Differentiation of the Cell Membrane:
The cell membrane may present regional differentiations that are related to specialized functions such as absorption, fluid transport, electrical coupling. Microvilli are found at the apical surface of the intestinal epithelium and form the brush border of the kidney tubules. They increase the absorption surface and are covered by a coat of glycoproteins.
Intercellular attachments comprise tight junctions, belt desmosomes, and spot desmosomes. Tight junctions serve to seal the intercellular spaces and to maintain the intercellular environment. They form a network of sealing strands below the apical regions of the cells. Belt desmosomes have a system of action and intermediate filaments and are situated below the zone of tight junctions.
These belt desmosomes represent the terminal bars or intermediary junctions of the old literature. Spot desmosomes are localized circular areas of mechanical attachment having two dense plaques with keratin tonofilaments. The number of spot desmosomes is correlated with the degree of mechanical stress that the tissue has to support e.g. epithelium of vagina is rich is spot desmosomes.
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Hemidesmosomes are found at the base of certain epithelia. Therefore similar to desmosomes in fine structure, but represent only half of them, the outer side frequently substituted with collagen fibrils.
Tight junctions are also known as zonula occludens, belt desmosomes as zonula adherens & spot desmosomes as macula adherenes.
(B) Gap Junctions & Intercellular Communications:
Cellular interactions are essential for the coordination of activities, and furthermore, the propagation between cells of signals for growth and differentiation is indispensable for development.
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It is now known that most cells in an organized tissue are interconnected by junctional channels and that they share a common pool of many small metabolites and ions that pass freely from one cell to another. Their individuality, however, is maintained by macromolecules that are not exchanged between cells.
The so called gap junctions (nexus) are essential in intercellular communications. They represent regions in which there are junctional channels through which ions and molecules can pass from one cell to another. Cells having gap junction are electrically coupled i.e. there is a free flow of electrical current carried by ions. At the gap junction the membranes are separated by a space of only 2 to 4 nm, and there is a hexagonal array of 8 to 9 nm particles.
At the centre of each particle there is a channel 1.5 to 2 nm in diameter. The macromolecular unit of the gap junction is called the connexon, which appears as annulus of six subunits surrounding the channel. It is thought that the sliding of the subunits causes the channel to open & close.
Gap junction provides direct intercellular communication by allowing the passage of molecules upto a limiting weight of 1300 to 1900 daltons fin chironomous salivary glands). The permeability is regulated by Ca++, if the intracellular Ca++ level increases, the permeability is reduced or abolished. Through the gap junction, metabolities (i.e., labeled nucleotides) can pass from one cell to another. In several strains of cancer cells, there is no coupling as seen in normal cultured cells.
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Coupling is genetically determined, and probably genes linked to one chromosome can correct the cancerous growth and the channel defect. Junctional communication may convey electrical signals between certain neurons (i.e. electrical synapses) and between cardiac cells, however, most neurons and skeletal muscle lack electrical coupling. Gap junctions are also used in the transfer of substances that control growth and differentiation in cells.
(C) Cell Coats and Cell Recognition:
Most cell membranes have a coat, sometimes referred to as glycocalyx, made of glycoproteins or polysaccharides. The cell coat is negatively charged and may bind Na+ and Ca++. Several cytochemical techniques are used to reveal the cell coats (e.g. PAS & ruthenium red). The oligosaccharidesmay be visualised by the use of lectins. The cell-coat is a kind of secretion product that undergoes an active turnover.
Extracellular materials lie outside the cell coat proper and the fuzzy layer of certain cells. In these extracellular materials collagens and glycosaminoglycans are the main components. There are polysaccharides, such as hyaluronic acid and chondroitin sulfate, in which there is a repeating disaccharide unit. These acidic molecules are associated with proteins forming proteoglycans.
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Many functions are attributed to the cell coat, like filtration, diffusion, protection of membrane. The cell coat makes a kind of microenvironment for the cell. It contains enzymes involved in the digestion of carbohydrates and proteins.
Molecular recognition between cells may depend on a molecular code made up of the individual monosaccharides such as galactose, hexosamine, mannose, fucose and sialic acid. The classical ABO blood groups are based on specific antigens of the red cell coat, which arc specified by their terminal carbohydrates.
Several other antigens are found on the cell-coat. Molecular recognition reaches maximum expression in the nervous tissue. Cell adhesion and cell dissociation and reassociation are dependent on cell coat. Cells are able to recognize similar cells in a tissue. In all cell recognition phenomena, the presence of specific carbohydrates at the membrane is essential.
From embryonic and adult animal tissues, low molecular weight proteins that act as plant lectins have been isolated. These animal lectins recognize saccharides on the cell surface and cause a p-galactoside hemoagglutination. Cells can also interact through diffusible substances acting at a distance. One such example is the life cycle of Dictyostelium discoideum, a slime mold in which the single amoeba may aggregate by the long range action of c AMP.
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(D) Cell Surface in Cancer Cells:
Cancer cells are characterized by uncontrolled growth, invasion and dissemination (metastasis). In a tumor all cancer cells are monoclonal. They may show changes in karyotype, increased glycolysis, and disorganization of cytoskeleton.
In cancer cells, there are many changes in the cell membrane and cell coat, such as the disappearance of gap junctions, loss of coupling, changes in glycolipids and glycoproteins and a reduction in gangliosides. There is also more mobility of surface receptors, increased transport of sugars, and growth of new antigens.
While in normal cells, the transport of iron and trace metal ions involves transferrin and transferrin receptors, in transformed cells there is an alternative
mechanism. Transformed cells secrete siderophore like growth factors (chelating agents that trap the metal ions), which compete with transferrin and transport the iron inside the cell.
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In the cell coat, fibronectin, a large glycoprotein found in “footprints” of moving cultured cells is reduced in cancer cells. A major characteristic of cancer cells is the combined loss of contact inhibition, motility and growth control, which is characteristics of normal cells in culture. Cancer cells are “immortal” and tend to pile up, while normale cells die after a number of divisions and tend to form monolayers.
A normal cell can be converted into a cancerous cell by a number of transforming agents, all of which affect the DNA and cause mutations. Different DNA and RNA viruses can produce transformation. Among the DNA viruses, polyoma and SV 40 are extensively used in experiments.
Adeno and Herpes virus (DNA) may also be involved. The RNA retroviruses are natural agents in animal tumors and can be transmitted to the offspring through the mother’s milk. In all these cases the viral genome becomes, integrated in certain regions of the host’s genome and is expressed in cancerous cells.