Lumican

Lumican, also known as LUM, is an is_associated_with::extracellular matrix is_associated_with::protein that, in humans, is encoded by the LUM is_associated_with::gene on chromosome 12.

Structure
Lumican is a is_associated_with::proteoglycan Class II member of the small leucine-rich proteoglycan (SLRP) family that includes is_associated_with::decorin, is_associated_with::biglycan, is_associated_with::fibromodulin, is_associated_with::keratocan, is_associated_with::epiphycan, and is_associated_with::osteoglycin. Like the other SLRPs, lumican has a molecular weight of about 40 kiloDaltons and has four major intramolecular domains:
 * 1) a signal peptide of 16 is_associated_with::amino acid residues;
 * 2) a negatively-charged N-terminal domain containing sulfated tyrosine and disulfide bond(s);
 * 3) ten tandem leucine-rich repeats allowing lumican to bind to other extracellular components such as collagen;
 * 4) a carboxyl terminal domain of 50 amino acid residues containing two conserved cysteines 32 residues apart.

There are four N-linked sites within the leucine-rich repeat domain of the is_associated_with::protein core that can be substituted with is_associated_with::keratan sulfate. The core protein of lumican (like is_associated_with::decorin and is_associated_with::fibromodulin) is horseshoe shaped. This enables it bind to is_associated_with::collagen molecules within a collagen fibril, thus helping keep adjacent fibrils apart.

Function
Lumican is a major is_associated_with::keratan sulfate is_associated_with::proteoglycan of the cornea but is ubiquitously distributed in most mesenchymal tissues throughout the body. Lumican is involved in collagen fibril organization and circumferential growth, is_associated_with::corneal transparency, and epithelial cell migration and tissue repair. Corneal transparency is possible due to the exact alignment of is_associated_with::collagen fibers by lumican (and is_associated_with::keratocan) in the intrafibrillar space.

Clinical significance
Mice that have the lumican gene knocked out (Lum-/-) develop opacities of the is_associated_with::cornea in both eyes and fragile is_associated_with::skin. The lumican (LUM) gene was thought to be a candidate susceptibility gene for high is_associated_with::myopia; however, a meta-analysis showed no association between LUM polymorphism and high myopia susceptibility in all genetic models studied.

Lum knockout mice also have abnormal is_associated_with::collagen in their is_associated_with::heart tissue, with fewer and thicker fibrils. Mice deficient in both lumican and is_associated_with::fibromodulin develop severe is_associated_with::tendinopathy (is_associated_with::tendon is_associated_with::pathology), revealing the importance of these SLRPs in the development of correctly sized and aligned is_associated_with::collagen fibers in is_associated_with::tendon. Along with other is_associated_with::extracellular matrix components, lumican expression was increased in equine is_associated_with::flexor is_associated_with::tendons six weeks after an injury.

Lumican is present in the is_associated_with::extracellular matrix of uteral tissues in fertile women. There is an increase of lumican during the proliferative to secretory phase of the is_associated_with::endometrium. In menopausal endometrial tissue, the level of lumican expression decreases and is also low in pathological compared to normal is_associated_with::endometrium.

Lumican is highly expressed in pleural effusions (is_associated_with::lung fluid) of patients with is_associated_with::adenocarcinoma. Its expression was low in is_associated_with::cancer cells but high in the is_associated_with::extracellular matrix surrounding the is_associated_with::tumor. Lumican expression was not associated with tumor grade or stage. In about half the patients with pancreatic ductal is_associated_with::adenocarcinoma tested, lumican in the is_associated_with::extracellular matrix around the is_associated_with::tumor was associated with a reduction in metastatic recurrence after surgery and with a three-fold longer survival than patients without stromal lumican. As lumican can directly bind to and inhibit is_associated_with::matrix metalloproteinase-14 (is_associated_with::MMP14), lumican may limit tumor progression by preventing is_associated_with::extracellular matrix is_associated_with::collagen is_associated_with::proteolysis by this is_associated_with::enzyme.