Current views on the possibility of cervical insufficiency correction

The main role in spontaneous abortion in 2nd and 3d trimesters is assigned to cervical insufficiency. According to a number of researchers, bed rest, elevated lower limbs, restriction of physical activity, tocolysis, antibacterial therapy do not affect the prolongation of pregnancy and are ineffective for preventing premature spontaneous labor. Correction of cervical insufficiency can be carried out by a vaginal form of progesterone, cerclage, pessary. The use of vaginal progesterone is justified in women with recurrent miscarriage, a history of premature birth, and shortening of the cervix to less than 25 mm. Indications for surgical correction are limited to patients with habitual loss of pregnancy due to cervical weakness or a history of premature birth. In the absence of significant obstetric history, cerclage has no advantages over the use of progesterone. The optimal time for cerclage is up to 20 weeks of pregnancy. Unlike progesterone cerclage has complications, the frequency and severity of which are attributable to the timing and indications for correction. Transabdominal cerclage is performed only when there is a technical impossibility of vaginal access due to the absence of a vaginal part of the cervix or after unsuccessful attempts of vaginal cerclages. Most often, the use of a pessary is associated with the diagnosis of a short cervix in terms of more than 24 weeks of gestation in the absence of an aggravated history. The combined use of gestagens, pessary and cerclage does not increase the efficiency of carrying a singleton pregnancy. Methods for the prevention of preterm delivery in multiple pregnancy, such as the introduction of a specialized outpatient service, bed rest, antibacterial therapy, progesterone, preventive cerclage or the insertion of a pessary do not change the incidence and mortality of newborns

HLA-B5/51 GENOTYPE: AN ASSOCIATION WITH THE CLINICAL MANIFESTATIONS OF BEHCET’S DISEASE

Objective: to estimate the contribution of HLA-B5/51 genotype to the clinical manifestations and risk of Behcet’s disease (BD) in two ethnic groups.Subjects and methods. 146 BD patients fulfilling the International Criteria for BD (ICBD) were divided into two ethnic groups: 1) 86 patients from Dagestan (representatives of 8 ethnic nationalities in this region) with mean age 30.7±9.6 years; disease duration – 8.8±10.1 years; 2) 60 ethnic Russian patients, nonresidents of Dagestan with mean age 32.9±11.1 years; disease duration – 11.2±10.1 years. All patients were examined at the V.A. Nasonova Research Institute of Rheumatology in 1990 to 2014. HLA class I antigens were typed by a microlymphocytotoxic technique using a Gisans anti-leukocyte sera kit (Saint Petersburg).Results. HLA-B5/51 was detected in 87 (59.6%) patients, much more often in men than in women (70 and 38%, respectively; p<0.01). Genital ulcers and erythema nodosum were significantly more common in HLA-B5/51-positive Dagestani (87.3 and 57%) than in HLA-B5/51-negative ones (56.5 and 26%; p=0.0019 and р=0.01; respectively). There were no significant differences in these signs in the Russian group of patients with BD depending on the presence of this allele. In HLA-B5/51-positive male Dagestani patients with BD, the risk of erythema nodosum was twice as high as that in HLA-B5/51-negative patients (p=0.054). In HLA-B5/51 female Dagestani carriers, the risk of genital ulcers and generalized uveitis proved to be 3.5 (p=0.057) and 2.7 times higher than that in HLA-B5/51 noncarriers. Frequency of HLA-B5/51 was 73.2% among the Dagestanis and 40% among the Russians. Furthermore, this investigation revealed HLA-B5/51 carriage mainly in the male BD patients. Therefore, in addition to ethnicity, gender should be borne in mind when analyzing the clinical associations with HLA-B5/51

Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation

The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding of how different peptides generate profound differences in G protein-mediated signalling is still lacking. Here we combine cryo-electron microscopy, molecular dynamics simulations, receptor mutagenesis and pharmacological assays, to interrogate the mechanism and consequences of GLP-1R binding to four peptide agonists; glucagon-like peptide-1, oxyntomodulin, exendin-4 and exendin-P5. These data reveal that distinctions in peptide N-terminal interactions and dynamics with the GLP-1R transmembrane domain are reciprocally associated with differences in the allosteric coupling to G proteins. In particular, transient interactions with residues at the base of the binding cavity correlate with enhanced kinetics for G protein activation, providing a rationale for differences in G protein-mediated signalling efficacy from distinct agonists

Факторы риска развития сахарного диабета 2-го типа у пациентов с подагрой: результаты проспективного исследования

The development of type 2 diabetes mellitus (DM) (DM2) in patients with gout can be influenced by both conventional and directly linked to gout risk factors (RFs).Objective: to identify RFs for the development of DM2 in patients with gout, including those directly associated with gout, based on long-term prospective follow-up data.Patients and methods. The study included 444 patients with gout older than 18 years (49 women, 395 men) who did not have DM. The followup period ranged from 2 to 8 years. The studied RFs for DM2 were: gender, age, family history of DM2, obesity, alcohol consumption >20 units per week, insufficient physical activity, unbalanced nutrition, history of hyperglycemia, coronary heart disease (CHD), arterial hypertension (AH), chronic heart failure, antihypertensive drugs, diuretics, glucocorticoids (GCs), urate-lowering therapy, serum levels of cholesterol, triglycerides, CRP, uric acid (UA), glucose, creatinine, glomerular filtration rate <60 ml/min/1.73 m2, the presence of tophi, >4 attacks of gout per year, ≥5 affected joints during the disease.Results and discussion. DM2 developed in 108 (24.3%) patients. These patients were older, had a family history of DM, more often received antihypertensive therapy, diuretics, and glucocorticoids (49.1; 73.1; 27.8 and 47.2%, respectively) than patients who did not develop DM2 (25.6; 50.5; 14.8 and 36.4%, respectively; p<0.05 for all cases). In addition, patients with DM2 were more likely to have subcutaneous tophi (59.3% versus 30.0%; p=0.001), among them there were more individuals (67.6% versus 31.6%; p=0.001) with frequent attacks of arthritis (>4 attacks per year). UA levels >480 and 600 μmol/l were also significantly more frequent (p=0.0002) in patients with DM2 (71.3 and 34.3%, respectively).According to logistic regression data, factors that increase the risk of developing DM2 were: family history of DM, a history of hyperglycemia, CHD, AH, intake of GCs, antihypertensive drugs, the presence of tophi, >4 exacerbations of gout per year. Febuxostat use and UA <300 μmol/L were associated with a lower risk of DM2.Conclusion. The occurrence of DM2 in gout is associated not only with well-known risk factors, but also with hyperuricemia and microcrystalline inflammation. Febuxostat therapy is associated with a lower risk of developing DM2.На развитие сахарного диабета (СД) 2-го типа (СД2) у пациентов с подагрой могут влиять как общепринятые, так и непосредственно связанные с подагрой факторы риска (ФР).Цель исследования – на основании данных многолетнего проспективного наблюдения выявить у пациентов с подагрой ФР развития СД2, в том числе непосредственно связанные с подагрой.Пациенты и методы. В исследование включено 444 пациента c подагрой старше 18 лет (49 женщин, 395 мужчин), не имевших СД. Длительность наблюдения составляла от 2 до 8 лет. В качестве ФР СД2 рассмотрены: пол, возраст, отягощенная наследственность по СД2, ожирение, употребление алкоголя >20 ед. в неделю, недостаточная физическая нагрузка, несбалансированное питание, гипергликемия в анамнезе, ишемическая болезнь сердца (ИБС), артериальная гипертензия (АГ), хроническая сердечная недостаточность, прием гипотензивных препаратов, диуретиков, глюкокортикоидов (ГК), уратснижающая терапия, сывороточные уровни холестерина, триглицеридов, СРБ, мочевой кислоты (МК), глюкозы, креатинина, скорость клубочковой фильтрации <60 мл/мин/1,73м2, наличие тофусов, >4 приступов подагры в год, ≥5 пораженных суставов за время болезни.Результаты и обсуждение. СД2 развился у 108 (24,3%) пациентов. Эти пациенты были старше, имели отягощенную наследственность по СД, чаще получали антигипертензивную терапию, диуретики и ГК (49,1; 73,1; 27,8 и 47,2% соответственно), чем больные, у которых СД2 не возник (25,6; 50,5; 14,8 и 36,4% соответственно; р<0,05 для всех случаев). Кроме того, у пациентов с СД2 чаще выявлялись подкожные тофусы (59,3% против 30,0%; р=0,001), среди них было больше лиц (67,6% против 31,6%; р=0,001) с частыми приступами артрита (>4 приступов в год). Уровни МК >480 и 600 мкмоль/л также значимо чаще (р=0,0002) определялись у больных с СД2 (71,3 и 34,3% соответственно).По данным логистической регрессии, факторами, увеличивающими риск возникновения СД2, были: наследственная отягощенность по СД, наличие гипергликемии в анамнезе, ИБС, АГ, прием ГК, гипотензивных препаратов, наличие тофусов, >4 обострений подагры в год. Прием фебуксостата и уровень МК <300 мкмоль/л ассоциировались с меньшим риском развития СД2.Заключение. Возникновение СД2 при подагре связано не только с общеизвестными ФР, но и с гиперурикемией и микрокристаллическим воспалением. Терапия фебуксостатом ассоциируется с меньшим риском развития СД2

Коморбидные инфекции у больных спондилоартритами: частота, структура, факторы риска

Objective: To investigate the frequency, structure, and risk factors of comorbid infections (CI) in patients with spondyloarthritis (SpA).Material and methods. The study included 332 patients with SpA. Patients were interviewed by the investigating physician, and additional information was obtained from medical records.Results and discussion. Respiratory tract (RT) and ear, nose, and throat (ENT) infections ranked first in the structure of CI. Exacerbation of SpA after CI was found in 42% of patients, and more severe CI against the background of SpA was found in 83 patients. 63 cases of severe CI (SCI) were documented, 63.5% of which were infections of the RT and ENT organs. Predictors for the development of lower RT (LRT) and ENT organ infections were the use of biologic disease-modifying antirheumatic drugs (bDMARDs) in general (odds ratio, OR 2.018; 95% confidence interval, CI 1.221-3.335; p=0.006 and OR 1.761; 95% CI 1.1-2.819, respectively; p=0.018) and tumor necrosis factor-α (TNF-α) inhibitors in particular (OR 2.376; 95% CI 1.417-3.983; p=0.001 and OR 1.833; 95% CI 1.123-2.994; p=0.015), and disease duration of more than 5 years (OR 1.774; 95% CI 1.034—3.042; p=0.037 and OR 2.22; 95% CI 1.378-3.576; p=0.001). The risk of developing LRT infection was higher in the presence of chronic lung disease (OR 3.673; 95% CI 1.602-8.425; p=0.002) and Charlesson Comorbidity Index ≥1 (OR 2.381; 95% CI 1.439-3.94; p=0.001), risk of developing ENT organ infections - with the use of >1 bDMARD (OR 2.4; 95% CI 1.199-4.804; p=0.013) and duration of methotrexate therapy over 5 years (OR 2.478; 95% CI 1.053-5.831; p=0.038). Risk factors for the development of SCI were the use of bDMARDs in general (OR 1.941; 95% CI 1.063-3.545; p=0.031) and TNFα in particular (OR 2.246; 95%, CI 1.218-4.139; p=0.01).Conclusion. The problem of CI in SpA is of great importance. The vast majority of patients with SpA should be vaccinated against pneumococcal infection and influenza.Цель исследования — изучить частоту, структуру и факторы риска коморбидных инфекций (КИ) у больных спондилоартритами (СпА).Материал и методы. В исследование включено 332 пациента со СпА. Больные были опрошены врачом-исследователем, дополнительную информацию получали из медицинской документации.Результаты и обсуждение. Ведущее место в структуре КИ занимали инфекции дыхательных путей (ДП) и ЛОР-органов. У 42% больных отмечено обострение СпА после перенесенной КИ, у 83 пациентов — более тяжелое течение КИ на фоне СпА. Документировано 63 случая серьезных КИ(СКИ), 63,5% из них — инфекции ДП и ЛОР-органов. Предикторами развития инфекций нижних ДП(НДП) и ЛОР-органов являлись применение генно-инженерных биологических препаратов (ГИБП) в целом (отношение шансов, ОШ 2,018; 95% Доверительный интервал, ДИ 1,221—3,335; р=0,006 и ОШ 1,761; 95% ДИ 1,1—2,819 соответственно; р=0,018) и ингибиторов фактора некроза опухоли α (иФНОα) в частности (ОШ 2,376; 95% ДИ 1,417—3,983;р=0,001 и ОШ 1,833; 95% ДИ 1,123—2,994; р=0,015), а также продолжительность заболевания более 5 лет (ОШ 1,774; 95% ДИ 1,034—3,042; р=0,037 и ОШ 2,22; 95% ДИ 1,378—3,576; р=0,001). Риск развития инфекций НДП был выше при наличии хронического заболевания легких (ОШ 3,673; 95% ДИ 1,602—8,425; р=0,002) и индекса коморбидности Чарльсона ≥1 (ОШ 2,381; 95% ДИ 1,439—3,94; р=0,001), риск развития инфекций ЛОР-органов — при использовании >1 ГИБП (ОШ 2,4; 95% ДИ 1,199—4,804; р=0,013) и длительности терапии метотрексатом более 5 лет (ОШ 2,478; 95% ДИ 1,053—5,831; р=0,038). Факторами риска развития СКИ были применение ГИБП в целом (ОШ 1,941; 95% ДИ 1,063-3,545;р=0,031) и иФНОα в частности (ОШ 2,246; 95% ДИ 1,218-4,139;р=0,01).Заключение. Проблема КИ при СпА является весьма актуальной. У подавляющего числа больных СпА необходимо проводить вакцинацию против пневмококковой инфекции и гриппа

Tissue distribution of the laminin β1 and β2 chain during embryonic and fetal human development

Laminins are the major glycoproteins present in all basement membranes. Previously, we showed that perlecan is present during human development. Although an overview of mRNA-expression of the laminin β1 and β2 chains in various developing fetal organs is already available, a systematic localization of the laminin β1 and β2 chains on the protein level during embryonic and fetal human development is missing. Therefore, we studied the immunohistochemical expression and tissue distribution of the laminin β1 and β2 chains in various developing embryonic and fetal human organs between gestational weeks 8 and 12. The laminin β1 chain was ubiquitously expressed in the basement membrane zones of the brain, ganglia, blood vessels, liver, kidney, skin, pancreas, intestine, heart and skeletal system. Furthermore, the laminin β2 chain was present in the basement membrane zones of the brain, ganglia, skin, heart and skeletal system. The findings of this study support and expand upon the theory that these two laminin chains are important during human development

Сравнительная эффективность тофацитиниба и адалимумаба у пациентов с псориатическим артритом в реальной клинической практике. Данные Общероссийского регистра пациентов с псориатическим артритом

Objective: to compare the clinical efficacy in real clinical practice of the targeted synthetic disease-modifying antirheumatic drug (sDMARD) tofacitinib (TOFA) and the biologic DMARD (bDMARD), an inhibitor of tumor necrosis factor alpha (TNFα), adalimumab (ADA) in patients with psoriatic arthritis (PsA), included in the Russian nationwide register of patients with PsA.Patients and methods. The study included 77 patients with PsA (43 men and 34 women) who met the CASPAR criteria and were observed in the Russian nationwide register. Patients were divided into two groups depending on the treatment. Group 1, in which oral TOFA was prescribed, 5 mg 2 times a day, included 41 patients: 24 (58.5%) men and 17 (41.5%) women, the median age was 41 [34; 50] years, the median duration of PsA was 72 [35; 120] months. Group 2, in which subcutaneous ADA was used, 40 mg every 2 weeks, included 36 patients: 19 (52.8%) men and 17 (47.2%) women, the median age was 44 [34; 51] years, the median duration of PsA was 59 [22; 102] months. Combination therapy, including methotrexate (MT), received 80.5% of patients in the TOFA group and 52.8% of patients in the ADA group. At the beginning of the study and every 6 months further, the activity and efficacy of PsA therapy were assessed in all patients according to DAPSA and criteria for minimal disease activity – MDA (number of painful joints ≤1, number of swollen joints ≤1, PASI ≤1 or BSA ≤3 , pain score ≤15, patient's general assessment of disease activity ≤20 mm on a visual analogue scale, HAQ ≤0.5, enthesitis ≤1), dynamics of BASDAI and BSA were also assessed. The number of patients who achieved remission (DAPSA ≤4) or MDA (5 criteria out of 7) during therapy with TOFA and ADA was determined.Results and discussion. Before the start of the therapy in the 1st group, the median DAPSA was 44.2 [37.8; 55.3]: moderate PsA activity was in 5 (12.2%) patients, high in 36 (87.8%) patients. In group 2, the median DAPSA was 35.8 [21.1; 52]: low activity was detected in 3 (8.6%), moderate – in 11 (31.4%), high – in 21 (60%) patients (data from 35 patients was available). 6 months after the start of treatment in patients of the 1st and the 2nd group, there was a significant decrease in all indicators of PsA activity compared to the baseline. The median DAPSA was 11 [4.3; 17.3] and 9.1 [6; 19.6]; remissions according to DAPSA reached 11 (26.8%) and 6 (20.8%) patients, respectively, low activity – 15 (36.6%) and 13 (44.8%), MDA – 16 (40%) and 9 (30%). The number of patients with dactylitis in the 1st and in the 2nd group significantly decreased: from 22 (53.7%) to 5 (13.2%) and from 13 (36.1%) to 6 (20%), respectively. Median HAQ decreased from 1 [0.625; 1.5] to 0.5 [0; 0.875] and from 0.875 [0.5; 1.38] to 0.5 [0; 0.875]; median BASDAI – from 6 [4.2; 7] to 1.4 [0.6; 3.2] and from 4.4 [1.9; 5.8] to 3 [0.8; 4.5], respectively. In group 1, the number of patients with BSA> 3% decreased from 16 (39%) to 8 (26.7%; p<0.225), and in group 2, due to insufficient data (5 patients), we failed to evaluate BSA dynamics.Conclusion. In real clinical practice TOFA and ADA both had comparable efficacy on all clinical manifestations of PsA: after 6 months of therapy, most patients with PsA achieved MDA, low disease activity and remission according to DAPSA and BASDAI.Цель исследования – сравнение клинической эффективности таргетного синтетического базисного противовоспалительного препарата (тсБПВП) тофацитиниба (ТОФА) и генно-инженерного биологического препарата (ГИБП), ингибитора фактора некроза опухоли α (иФНОα) адалимумаба (АДА) у больных псориатическим артритом (ПсА) в реальной клинической практике по данным Общероссийского регистра пациентов с ПсА.Пациенты и методы. В исследование включено 77 больных ПсА (43 мужчины и 34 женщины), соответствовавших критериям CASPAR и наблюдавшихся в Общероссийском регистре. Пациенты были разделены на две группы в зависимости от проводимого лечения. В 1-ю группу, в которой назначали таблетированный ТОФА по 5 мг 2 раза в день, вошел 41 пациент: 24 (58,5%) мужчины и 17 (41,5%) женщин, медиана возраста – 41 [34; 50] год, медиана длительности ПсА – 72 [35; 120] мес. Ко 2-й группе, в которой использовали АДА по 40 мг/2 нед подкожно, отнесены 36 больных: 19 (52,8%) мужчин и 17 (47,2%) женщин, медиана возраста – 44 [34; 51] года, медиана длительности ПсА – 59 [22; 102] мес. Комбинированную терапию, включавшую метотрексат (МТ), получали 80,5% пациентов группы ТОФА и 52,8% пациента группы АДА. У всех пациентов в начале исследования и каждые 6 мес оценивали активность и эффективность терапии ПсА по DAPSA и критериям минимальной активности болезни – MAБ (число болезненных суставов ≤1, число припухших суставов ≤1, PASI ≤1 или BSA ≤3, оценка боли ≤15, общая оценка активности болезни больным ≤20 мм по визуальной аналоговой шкале, HAQ ≤0,5, энтези- ты ≤1), динамику BASDAI и BSA. Определяли число больных, достигших ремиссии (DAPSA ≤4) или МАБ (5 критериев из 7) на фоне терапии ТОФА и АДА.Результаты и обсуждение. До начала терапии в 1-й группе медиана DAPSA составляла 44,2 [37,8; 55,3]: умеренная активность ПсА была у 5 (12,2%), высокая – у 36 (87,8%) больных. Во 2-й группе медиана DAPSA равнялась 35,8 [21,1; 52]: низкая активность выявлена у 3 (8,6%), умеренная – у 11 (31,4%), высокая – у 21 (60%) больного (доступны данные 35 пациентов). Через 6 мес после начала лечения у пациентов 1-й и 2-й групп произошло значимое снижение всех показателей активности ПсА по сравнению с исходными. Мeдиана DAPSA составила соответственно 11 [4,3; 17,3] и 9,1 [6; 19,6]; ремиссии по DAPSA достигли соответственно 11 (26,8%) и 6 (20,8%) больных, низкой активности – 15 (36,6%) и 13 (44,8%), МАБ – 16 (40%) и 9 (30%). Число пациентов с дактилитом значимо уменьшилось: с 22 (53,7%) до 5 (13,2%) и с 13 (36,1%) до 6 (20%) соответственно в 1-й и 2-й группах. Мeдиана HAQ снизилась с 1 [0,625; 1,5] дo 0,5 [0; 0,875] и с 0,875 [0,5; 1,38] дo 0,5 [0; 0,875]; мeдиана BASDAI – с 6 [4,2; 7] дo 1,4 [0,6; 3,2] и с 4,4 [1,9; 5,8] дo 3 [0,8; 4,5] соответственно. В 1-й группе число пациентов с BSA >3% сократилось с 16 (39%) до 8 (26,7%; p<0,225), а во 2-й группе из-за недостаточного объема данных (5 пациентов) динамику BSA оценить не удалось.Заключение. Показана сопоставимая эффективность ТОФА и АДА в реальной клинической практике в отношении всех клинических проявлений ПсА: через 6 мес терапии у большинства пациентов с ПсА отмечено достижение МАБ, низкой активности болезни и ремиссии по DAPSA и BASDAI

Endogenous laminin is required for human airway smooth muscle cell maturation

BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes

Matricellular Proteins Produced by Melanocytes and Melanomas: In Search for Functions

Matricellular proteins are modulators of cell-matrix interactions and cellular functions. The group includes thrombospondin, osteopontin, osteonectin/SPARC, tenascin, disintegrins, galectins and CCN proteins. The production of matricellular proteins such as osteopontin, SPARC or tenascin is highly upregulated in melanoma and other tumors but little is known about their functions in tumor growth, survival, and metastasis. The distribution pattern of CCN3 differs from most other matricellular proteins, such that it is produced abundantly by normal melanocytes, but is not significantly expressed in melanoma cells. CCN3 is known to inhibit melanocyte proliferation and stimulate adhesion to collagen type IV, the main component of the basement membrane. CCN3 has a unique role in securing adhesion of melanocytes to the basement membrane distinct from other melanoma-produced matricellular proteins which act as de-adhesive molecules and antagonists of focal adhesion. Qualitative and quantitative changes in matricellular protein expression contribute to melanoma progression similar to the E-cadherin to N-cadherin class switch, allowing melanoma cells to escape from keratinocyte control