MUC2, MUC5AC and MUC5B in the mucus of a patient with pseudomyxoma peritonei: Biochemical and immunohistochemical study

Mall, Anwar Suleman; Chirwa, Nthato; Govender, Dhirendra; Lotz, Zoë; Tyler, Marilyn; Rodrigues, Jerry; Kahn, Delawir; Goldberg, P. A.

doi:10.1111/j.1440-1827.2007.02137.x

Cited by 28 publications

(35 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The prognostic significance of MUC2 is reported to be controversial, as the expression level of MUC2 in PMP is independent of the degree of the malignant transformation [130]. The presence of MUC5B, in addition to MUC2 and MUC5AC was reported in case studies of PMP subjects [131,132], investigations by Sheehan et al implicated a low-charge glycoform of MUC5B in the production of a tenacious respiratory mucus plug [133,134], it may be MUC5B as speculated by Mall et al that is responsible for the semisolid material found in some PMP patients. The development of mucin-targeted therapies was suggested by Amini et al [127] which could be a promising avenue for future research based on the relevance of MUC2, MUC5AC and MUC5B in PMP.…”

Section: Pseudomyxoma Peritoneimentioning

confidence: 98%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

View full text Add to dashboard Cite

Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

show abstract

Section: Pseudomyxoma Peritoneimentioning

confidence: 98%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In two case studies, Mall et al reported the presence of MUC5B, in addition to MUC2 and MUC5AC, in the PMP material [122,123]. Based on the investigations by Sheehan et al implicating a low-charge glycoform of MUC5B in the production of a tenacious respiratory mucus plug [124,125], Mall et al speculated that it may be MUC5B that is responsible for the semisolid material found in some PMP patients.…”

Section: Introductionmentioning

confidence: 99%

“…Based on the investigations by Sheehan et al implicating a low-charge glycoform of MUC5B in the production of a tenacious respiratory mucus plug [124,125], Mall et al speculated that it may be MUC5B that is responsible for the semisolid material found in some PMP patients. Given the high protein content of the PMP secretions, they also raised the possibility that interactions between mucin and non-mucin proteins could contribute to the viscous nature of the PMP exudates [122,123]. Table 3 summarizes a number of studies in which disease-specific expression pattern of MUC2 and other mucins in PMP has been explored.…”

Section: Introductionmentioning

confidence: 99%

Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects

Amini

Masoumi-Moghaddam

Ehteda

et al. 2014

Orphanet J Rare Dis

View full text Add to dashboard Cite

Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1–2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as the secreted mucins of relevance in PMP. Development of mucin-targeted therapies could be a promising avenue for future research which is addressed in this article.

show abstract

“…It has previously been reported that pseudomyxoma peritonei (PMP), which was first described in 1842, is a disease of MUC2-expressing goblet cells, although the copious intraperitoneal mucinous ascites containing huge globules of extracellular mucin [11, 12] may also contain MUC5AC [13]. The accumulation of large amounts of extracellular mucus in the abdominal cavity is probably the main cause of the disease's morbidity and mortality, irrespective of the site of origin [12].…”

Section: Introductionmentioning

confidence: 99%

“…The accumulation of large amounts of extracellular mucus in the abdominal cavity is probably the main cause of the disease's morbidity and mortality, irrespective of the site of origin [12]. The first and only report, to our knowledge, of the presence of MUC5B in tissue and gelatinous material of a 58-year-old male diagnosed with PMP was from our laboratory [13]. The expression of MUC2 in PMP accounts for both the voluminous deposits of extracellular mucus and in women would help distinguish the appendix rather than the ovary as the site of origin of the disease [14].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical and Biochemical Characterization of Mucin in Pseudomyxoma Peritonei: A Case Study

Mall¹,

Lotz²,

Tyler³

et al. 2011

Case Rep Gastroenterol

Self Cite

View full text Add to dashboard Cite

We previously reported the presence of MUC2, MUC5AC and, for the first time, MUC5B in a 58-year-old male with pseudomyxoma peritonei (PMP). This is a report on the biochemical and immunohistochemical characterization of mucin in a 50-year-old female with the same rare illness. A right oophorectomy and appendicectomy and a resection of the involved omentum were performed. Approximately a litre of crude material in the sol and gel phases was obtained from the patient during laparotomy. This was briefly homogenized in 6 M guanidinium hydrochloride and proteolytic inhibitors and purified by density gradient centrifugation in caesium chloride. At laparotomy it was noted that the patient had appendiceal and ovarian masses as well as extensive mucinous deposits in the omentum and peritoneum. A mucinous adenocarcinoma of the appendix and ovary was confirmed on histology. The cells expressed both sulphated and non-sulphated acidic mucins. The presence of MUC2, MUC5AC, MUC5B and α-1-acid glycoprotein was shown by Western blotting and MUC4 by immunohistochemical staining. MUC1 and MUC6 were not detectable in the tissue. The study confirms that MUC2, MUC5AC and MUC5B are produced in the mucus of patients with PMP. The expression of MUC4 in this disease has not been previously reported.

show abstract

MUC2, MUC5AC and MUC5B in the mucus of a patient with pseudomyxoma peritonei: Biochemical and immunohistochemical study

Cited by 28 publications

References 45 publications

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects

Immunohistochemical and Biochemical Characterization of Mucin in Pseudomyxoma Peritonei: A Case Study

Contact Info

Product

Resources

About