Sanford-Burnham Scientists Identify Natural Compound that Inhibits Cancer Cell Migration. Molecule found in sea sponges may help control metastasis. Investigators at Sanford-Burnham Medical Research Institute (Sanford-Burnham, formerly Burnham Institute for Medical Research) led by Kristiina Vuori, M.D., Ph.D., have discovered that the natural compound sceptrin, which is found in marine sponges, reduces cancer cell motility (movement) and has very low toxicity. Metastasis is one of the deadliest aspects of cancer, so restricting aberrant cell movement is an important step towards advancing treatments. The research was published online in ACS Chemical Biology, in collaboration with Phil S. Baran, Ph.D., of The Scripps Research Institute. The team tested sceptrin in multiple tumor cell types, including cervical, breast and lung cancers. Sceptrin restricted motility in all cell lines. Further tests showed the compound works by limiting the cells’ ability to contract, a critical function for cell motility. The researchers also found that sceptrin synthesized in the laboratory was just as effective at combating motility as the naturally-derived compound. “Given the recently achieved synthesis of sceptrin in multi-gram quantities by the Baran laboratory, sceptrin could prove to be an attractive lead molecule for further preclinical testing and development for
therapeutic purposes,” said Dr. Vuori. “It may also prove to be a useful research tool in order to elucidate the mechanisms involved in cell motility.” The researchers cultured growing cancer cells with growth factor to encourage motility. These cells were treated with varying amounts of sceptrin, which was found to be more effective at increased concentrations. Subsequently, the team conducted apoptosis and cell proliferation studies to determine whether these mechanisms accounted for the decrease in motility of sceptrin-treated cells. Other assays determined that sceptrin limits motility by reducing cell contractility. news from sanfordburnham.org – Sponges are animals of the phylum Porifera. Their bodies consist of jelly-like mesohyl sandwiched between two thin layers of cells. While all animals have unspecialized cells that can transform into specialized cells, sponges are unique in having some specialized cells that can transform into other types, often migrating between the main cell layers and the mesohyl in the process. Sponges do not have nervous, digestive or circulatory systems. Instead, most rely on maintaining a constant water flow through their bodies to obtain food and oxygen and to remove wastes, and the shapes of their bodies are adapted to maximize the efficiency of the water flow. All are sessile aquatic animals and, although there are freshwater species, the great majority are marine (salt water) species, ranging from tidal zones to depths exceeding 8,800 metres (5.5 mi). While most of the approximately 5,000 known species feed on bacteria and other
food particles in the water, some host photosynthesizing micro-organisms as endosymbionts and these alliances often produce more food and oxygen than they consume. A few species of sponge that live in food-poor environments have become carnivores that prey mainly on small crustaceans.Sponges are known for regenerating from fragments that are broken off, although this only works if the fragments include the right types of cells. A few species reproduce by budding. When conditions deteriorate, for example as temperatures drop, many freshwater species and a few marine ones produce gemmules, “survival pods” of unspecialized cells that remain dormant until conditions improve and then either form completely new sponges or re-colonize the skeletons of their parents. However most sponges use sexual reproduction, releasing sperm cells into the water. In viviparous species the cells that capture most of the adults’ food capture the sperm cells but, instead of digesting them, transport them to ova in the parent’s mesohyl. The fertilized eggs begin development within the parent and the larvae are released to swim off in search of places to settle. In oviparous species both sperm and egg cells are released into the water and fertilisation and development take place outside the parent’s bodies.Sponges use various materials to reinforce their mesohyl and in some cases to produce skeletons, and this forms the main basis for classifying sponges. Calcareous sponges produce spicules made of calcium carbonate. Demosponges reinforce the mesohyl with fibers of a
special form of collagen called spongin, most also produce spicules of silica, and a few secrete massive external frameworks of calcium carbonate. Although glass sponges also produce spicules made of silica, their bodies mainly consist of syncytia that in some ways behave like many cells sharing a single external membrane, and in others like individual cells with multiple nuclei. Probably because of their variety of construction methods, demosponges constitute about 90% of all known species, including all freshwater ones, and have the widest range of habitats. Calcareous sponges are restricted to relatively shallow marine waters where production of calcium carbonate is easiest. The fragile glass sponges are restricted to polar regions and the ocean depths where predators are rare, and their feeding systems very efficiently harvest what little food is available. Fossils of all of these types have been found in rocks dated from 580 to 523 million years ago. In addition Archaeocyathids, whose fossils are common in rocks from 530 million years ago but not after 490 million years ago, are now regarded as a type of sponge.It is generally thought that sponges’ closest single-celled relatives are choanoflagellates, which strongly resemble the cells that sponges use to drive their water flow systems and capture most of their food. It is also generally agreed that sponges do not form a monophyletic group, in other words do not include all and only the descendants of a common ancestor, because it is thought that Eumetazoa (more complex animals) are descendants of a sub-group of sponges. However it is uncertain
which group of sponges is closest to Eumetazoa, as both calcareous sponges and a sub-group of demosponges called Homoscleromorpha have been nominated by different researchers. In addition a study in 2008 suggested that the earliest animals may have been similar to modern comb jellies. Since comb jellies are considerably more complex than sponges, this would imply that sponges had mobile ancestors and greatly simplified their bodies as they adapted to a sessile filter feeding lifestyle. Chancelloriids, sessile, bag-like organisms whose fossils are found only in rocks from the Cambrian period, increase the uncertainty as it has been suggested that they were sponges but also that their external spines resemble the “chain mail” of the slug-like Halkieriids.The few species of demosponge that have entirely soft fibrous skeletons with no hard elements have been used by humans over thousands of years for several purposes, including as padding and as cleaning tools. However by the 1950s these had been over-fished so heavily that the industry almost collapsed, and most sponge-like materials are now synthetic. Sponges and their microscopic endosymbionts are now being researched as possible sources of medicines for treating a wide range of diseases. Dolphins have been observed using sponges as tools while foraging. Antibiotic compounds; Sponges have medicinal potential due to the presence in sponges themselves or their microbial symbionts of chemicals that may be used to control viruses, bacteria, tumors and fungi.
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