Anti-mucin Monoclonal Antibodies Research Articles

Elemental diet moderates 5-fluorouracil-induced gastrointestinal mucositis through mucus barrier alteration.

There are reports that elemental diet (ED) ameliorates oral mucositis caused by antineoplastic chemotherapy. Although this effectiveness may be partly due to high nutrient absorption, the effects of chemotherapy on mucosal defense mechanisms remain unclear. We investigated the effects of oral supplementation with ED on mucin in 5-fluorouracil (5-FU)-induced intestinal mucositis. 5-FU was administered to rats orally once daily, and ED was supplied orally twice daily for 5 days. The severity of mucositis was assessed by length, dry tissue weight, and villus height of the intestinal tract. Using anti-mucin monoclonal antibody, we compared the immunoreactivity in the gastrointestinal (GI) tract and mucin content by histological and biochemical examinations. Oral supplementation with ED reduced histological damage and loss of length, dry tissue weight, and villus height induced by 5-FU administration. ED markedly altered PGM34 antibody immunoreactivity and mucin contents in the small intestine of rats with 5-FU-induced mucositis. ED may possibly be more effective for the prevention of antineoplastic chemotherapy-induced mucositis through the activation of GI mucus cells.

Induction of Sda-sialomucin and sulfated H-sulfomucin in mouse small intestinal mucosa by infection with parasitic helminth

Mucin is a major component of mucus on gastrointestinal mucosa. Mucin alteration in the host is considered to be the principal event for expulsion of intestinal helminths. However, it is unclear what mucin alterations are induced by various helminth infections. In this study, the alterations of mouse small intestinal mucin after infection with two nematodes, Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which parasitize the jejunal epithelium, and a cestode, Vampirolepis nana, which parasitizes the ileal epithelium, were examined biochemically and histologically using two anti-mucin monoclonal antibodies (mAbs), HCM31 and PGM34, which recognize Sda antigen, NeuAcα2–3(GalNAcβ1–4)Galβ1-4GlcNAcβ-, and sulphated H type 2 antigen, Fucα1-2Galβ1-4GlcNAc(6SO3H)β-, respectively. The goblet cell mucins that reacted with HCM31 increased conspicuously on the jejunal mucosa concurrently with expulsion of N. brasiliensis. Increased levels of HCM31-reactive mucins were observed in the jejunal mucosa after H. polygyrus infection, despite the ongoing parasitism. Goblet cell mucins that reacted with PGM34 increased on the ileal mucosa during V. nana parasitism. Small intestinal goblet cells reacting with the two mAbs were not observed in non-infected mice, although sialomucins and sulfomucins were abundantly present. Additionally, the number of ileal goblet cells that reacted with the two mAbs was increased at the time of expulsion of heterophyid trematode. These results indicate that the type of specific acidic mucins expressed after infection varies among species of intestinal helminth, and, furthermore, that the relationship with worm expulsion is also different.

Changes in the Mucus Barrier during Cisplatin-Induced Intestinal Mucositis in Rats

Aim. Gastrointestinal mucositis is a frequent complication of antineoplastic chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms remain poorly understood. We studied the effects of cisplatin on mucin, one of the principal defense factors of the gastrointestinal mucosa, and evaluated the efficacy of two different types of H2-receptor antagonists against cisplatin-induced mucositis. Methods. Cisplatin (6 mg/kg) was administered intravenously to rats (day 0). The rats were sacrificed 1, 3, 7, and 11 days after treatment, and their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg) or lafutidine (30 mg/kg) was given orally once daily on days 0, 1, and 2. Histological and biochemical findings were compared among the groups to assess effects on cisplatin-induced injury. Results. Cisplatin significantly altered the immunoreactivity and content of mucin in the small intestinal mucosa, especially in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and attenuated decreased mucin accumulation. Conclusion. Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells.

Use of the monoclonal antibody PAM4 to differentiate pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis and benign nonmucinous cysts of the pancreas.

188 Background: Previous studies have demonstrated that anti-mucin monoclonal antibody (mAb) PAM4 is highly specific for PDAC and its precursor lesions. To investigate specificity further, we examined the expression of PAM4-reactive mucin in chronic pancreatitis and benign non-mucinous cystic lesions of the pancreas. Methods: A tissue microarray of PDAC (N=14), as well as surgical specimens from chronic pancreatitis (N=32) and benign non-mucinous cystic lesions of the pancreas (N=19), were assessed by immunohistochemistry for expression of the PAM4-reactive mucin, as well as MUC1 (mAb-MA5), MUC4 (mAb-8G7), and CEACAM6 (mAb-MN-15). Results: PAM4-reactive mucin, MUC1, MUC4 and CEACAM6 were expressed in 79% (11/14), 100% (14/14), 86% (12/14) and 100% (14/14) of invasive pancreatic adenocarcinoma. PAM4 only weakly labeled 6% (1/19) of benign non-mucinous cystic lesions, 1 of 15 serous cystadenomas (SCAs) and 0 of 4 cysts with squamous epithelial lining (2 lymphoepithelial cysts, and 2 retention cysts with squamous metaplasia). However, the expression of MUC1, MUC4 and CEACAM6 was detected in 53% (8/15), 0% (0/15) and 13% (2/15) of SCAs, and in 4, 3 and 3 of the 4 cysts with squamous epithelial lining, respectively. PAM4 labeled 19% (6/32) of chronic pancreatitis specimens; however, this PAM4 reactivity was restricted to the PanIN precursor lesions associated with chronic pancreatitis. Inflamed tissue was negative. The expression of MUC1, MUC4 and CEACAM6 was detected in 90% (27/30), 78% (25/32), and 97% (31/32) of chronic pancreatitis. In all of the positively-labeled specimens, the reactivity was present in non-neoplastic inflamed pancreatic tissue in addition to PanIN. Conclusions: The expression of PAM4 was detected in only 6% of benign non-mucinous cystic lesions and in the precursor lesions associated with chronic pancreatitis. These results suggest that PAM4, in contrast to MUC1, MUC4, and CEACAM6, may be useful to differentiate benign non-mucinous cystic lesions of the pancreas and chronic pancreatitis from PDAC. (Supported in part by NIH grant CA096924.)

Different effects of two types of H2-receptor antagonists, famotidine and roxatidine, on the mucus barrier of rat gastric mucosa

Compared with the aggressive factors, little attention has been paid to the mucosal defensive factors in ulcer therapy, and the role of the H2-receptor antagonists in gastric mucosal protection has not been well characterized. In the present study, the effects of different types of H2-receptor antagonists (famotidine and roxatidine) on rat gastric mucus cells were investigated using both biochemical and histological methods. Each drug (famotidine, 3 mg/kg; roxatidine, 100 mg/kg) was orally administered to rats by gavage once daily for 7 days. The biosynthesis and tissue content of mucin were compared in the gastric mucosa treated with each drug. Using anti-mucin monoclonal antibodies, the mucin content and immunohistochemical localization were also compared. Both the biosynthesis and the accumulation of gastric mucin were significantly decreased in the famotidine-treated rats, but not in the roxatidine. Both the content and the immunoreactivity of surface mucus cell-derived mucin were reduced by famotidine, while they were maintained in roxatidine-treated rat stomachs. There was no difference between the groups in the content and immunoreactivity of mucous neck cell-derived mucin. H2-receptor antagonists should be classified in relation to gastric surface mucus cell function, raising the possibility of more effective ulcer therapy.

Vulnerable Sites and Changes in Mucin in the Rat Small Intestine After Non-steroidal Anti-inflammatory Drugs Administration

The location of mucosal damage and changes in mucin content in the rat small intestine following administration of non-steroidal anti-inflammatory drugs (NSAIDs) have not been well elucidated. After subcutaneous administration of loxoprofen sodium (10-40 mg/kg), the small intestinal mucosa of male Wistar rats was evaluated macroscopically, histologically, and immunohistochemically by measuring the total mucin content and immunoreactivity for anti-mucin monoclonal antibody, HCM31, 1, 3, 7, and 14 days later. Changes in the number of enterobacteria invading the mucosa around the lesions were also determined. Loxoprofen sodium induced erosions and ulcers along the mesenteric margin of the distal jejunum. Early (≤6 h) mucosal lesions were small and round, located between the branches of the mesenteric arteries. In the jejunum, there was a transient increase in the total mucin content, and HCM31-positive mucin in the mucosa around the ulcers increased significantly on days 3 and 7, but in the ileum there were no marked changes and few ulcers. Bacterial translocation following loxoprofen sodium administration significantly increased, according to the site of the intestinal lesions. Vascularly compromised sites along the jejunal mesenteric margin are vulnerable to NSAIDs-induced damage and show increased numbers of enterobacteria in the NSAIDs-treated mucosa. Increased sialomucin content in the mucus around the lesions may play an important role in the healing of NSAIDs-induced intestinal lesions.

Nippostrongylus brasiliensis: Increase of sialomucins reacting with anti-mucin monoclonal antibody HCM31 in rat small intestinal mucosa with primary infection and reinfection

Infections with the parasitic helminth, Nippostrongylus brasiliensis, cause changes in rat small intestinal goblet cell mucin, particularly in the peripheral sugar residues of oligosaccharide. These changes may correlate with expulsion. In this study, we examined changes in mucin oligosaccharides caused by primary infection and reinfection with N. brasiliensis, using two monoclonal antibodies, HCM31 and PGM34, that react with sialomucin and sulfomucin, respectively. Enzyme-linked immunosorbent assay of jejunal mucins showed that the relative reactivity of mucins with HCM31, but not PGM34, increased up to 16 days after primary infection and 6 days after reinfection, the times when the worms were expelled from the rats. Immunohistochemical studies confirmed that goblet cells stained with HCM31 greatly increased at the time of worm expulsion. These results indicate that the marked increase observed in HCM31-reactive sialomucins may be related to expulsion of the worms.

Effects of indomethacin on the rat small intestinal mucosa: immunohistochemical and biochemical studies using anti-mucin monoclonal antibodies

The luminal surface of the gastrointestinal tract is covered by a viscoelastic gel layer that acts as a protective barrier against the intraluminal environment. Because the situation of the small intestine has not been elucidated to the same degree as other sections, in this study, we investigated the effects of indomethacin on the rat small intestinal mucosa. Male Wistar rats were given indomethacin 10 mg/kg s-c and sacrificed 1, 3, 7, or 14 days later. The small intestine was opened along the anti-mesenteric side, and examined macroscopically. Total mucin content in the small intestinal epithelium was measured and immunoreactivity was examined using anti-mucin monoclonal antibodies HCM31 and PGM34. Indomethacin caused punched out and linear ulcers located mostly along the mesenteric margin of the distal jejunum with sparing of the ileum. Histological examination showed sialomucin recognized by HCM31 increased on day 3 especially in the regenerating epithelium around the ulcer edge. Furthermore, the surface mucous gel layer displayed a multilaminated pattern, consisting of non-sulfated sialomucin-rich layers and sulfated mucin-rich layers, where both mucins had the common core protein, MUC2. Biochemical measurements also showed the total mucin content of the jejunum increased transiently and HCM31-positive mucin increased approximately 4 times greater than baseline on day 3, but no marked changes were observed in the ileum, with few ulcers observed. Indomethacin administration causes quantitative and qualitative change in jejunal mucin. In particular, sialomucin plays an important role in regenerating epithelium during the healing process following indomethacin-induced mucosal damage.

Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa

In Japan, peptic ulcer disease (PUD) is treated clinically with a combination of a mucosal protectant and acid suppressants, but there is scant information regarding the effects of these drugs on normal gastric mucus cells. In the present study, the effects of co-administration of methylmethionine sulfonium chloride (MMSC) and famotidine on rat gastric mucus cells were investigated using both biochemical and histological methods. Rats were divided into four groups: controls were given carboxymethylcellulose orally once daily for 7 days and the second, third and fourth groups were treated similarly with famotidine (famotidine group), MMSC (MMSC group) or famotidine plus MMSC (combination group). After killing the rats on the 8th day, the stomachs were removed and the biosynthesis and amount of mucin in different areas of the gastric mucosa were compared among groups. Using anti-mucin monoclonal antibodies, the mucin content and immunoreactivity were also compared. Both the biosynthesis and accumulation of mucin were significantly decreased in the famotidine group, but increased in the MMSC and combination groups. The amount and immunoreactivity of surface mucus cell-derived mucin were both reduced in the famotidine group, and increased in the MMSC and combination groups. There was no difference among the groups in the content and immunoreactivity of gland mucus cell-derived mucin. Famotidine-induced suppression of gastric surface mucus cell function is prevented by combined treatment with MMSC, raising the possibility of a more effective cure of PUD.

Effects of Tea Catechins on the Gastrointestinal Mucosa in Rats

Although tea catechins are known to exert a potent antiulcer effect on the alimentary tract, there is scant information concerning their effects on normal mucus cell functions. Using original anti-mucin monoclonal antibodies, we studied the influences of long-term administration of catechins on the quantity and quality of mucin in rat gastrointestinal mucosa. Administration of 0.5% tea catechins significantly increased the mucin content of the ileum, but not the stomach. An enzyme-linked immunosorbent assay (ELISA) showed no remarkable qualitative changes in gastric mucin, but a selective increase and decrease in sulfo- and sialomucins, respectively, in the ileum of rats administered catechins. The ELISA results were consistent with both the immunohistochemical findings and the high-iron diamine-alcian blue staining pattern. These findings indicate that tea catechins modulate ileal mucin metabolism in the ileal mucosa, suggesting that further studies focusing on the ileal epithelium will assist in further elucidation of the mechanism of catechin effects.

Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis

Objective. Acid antisecretory agents are used for the prophylaxis of cancer chemotherapy (CT)-induced gastrointestinal (GI) mucositis. Although these drugs seem to be clinically beneficial, data on their effects on the GI mucosal defense during CT treatment are scant. The objective of this study was to compare the effects of omeprazole, lansoprazole, and lafutidine on mucin, a major mucus component, during 5-fluorouracil (5-FU) treatment, as a CT regimen. Material and methods. Rats, weighing approximately 230 g, were divided into five groups. The control group was administered 0.5% carboxymethylcellulose orally once daily for 5 days. The second, third, fourth, and fifth groups were treated with 5-FU (50 mg/kg), 5-FU plus omeprazole (10 mg/kg), 5-FU plus lansoprazole (10 mg/kg), and 5-FU plus lafutidine (30 mg/kg) in the same way, respectively. The rats were sacrificed on the sixth day, and their stomachs and small intestines were removed. Using anti-mucin monoclonal antibodies, we compared the immunoreactivity in different areas of the rats’ GI tracts as well as the mucin content. Results. Body-weight decreased in rats in the 5-FU group. Lafutidine, but neither omeprazole nor lansoprazole, inhibited the 5-FU-induced weight loss. Mucosal damage and reduced mucin content in stomach and small intestine were observed in rats receiving 5-FU alone. In the stomach, all antisecretory drugs caused the protective effects against 5-FU-induced mucosal injury and alleviation of the decreased mucin accumulation. In the jejunum and ileum, lafutidine, but neither omeprazole nor lansoprazole, ameliorated the 5-FU-induced mucosal damage and decreased mucin accumulation. Conclusion. Lafutidine could offer the possibility of more effective prevention of CT-induced mucositis through the activation of GI mucus cells.

Changes in the mucus barrier of the rat during 5-fluorouracil-induced gastrointestinal mucositis

Objective. A frequent complication of antineoplastic chemotherapy (CT) is gastrointestinal (GI) mucositis. Although clinically this mucositis can be treated, data on the effect of CT on the mucosal defense mechanisms are scant, so the effects of 5-fluorouracil (5-FU) on mucin, one of the principal defense factors of the GI mucosa, were investigated. Material and methods. 5-FU was administered orally to rats at a dose of 50 mg/kg once daily for 5 days. Using anti-mucin monoclonal antibodies, the immunoreactivity in different areas of the rats’ GI tracts was compared, as well as the mucin content. Changes in the GI mucin during the process of recovery from the injury were also investigated. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) was used to determine whether or not the effects of 5-FU on cell proliferation contributed to the changes in mucin. Results. 5-FU caused significant alterations of the immunoreactivity and content of mucin in the rat GI mucosa, especially in the jejunum. The jejunal mucin content was most markedly reduced on day 1 after drug withdrawal, and increased thereafter. By day 7, the content had transiently but significantly increased approximately 1.5-fold, and returned to the basal level by day 13. The number of PCNA-positive cells strikingly decreased at day 1, but by day 7 had increased approximately 2-fold, compared with the control. Conclusion. The activation of mucus cells in the jejunum, if appropriately manipulated, could lead to more effective prevention of CT-induced GI mucositis.

Protective Effects of the Whisky Congeners on Ethanol‐Induced Gastric Mucosal Damage

The ingestion of both ethanol and whisky can induce acute gastrointestinal bleeding. The effects of the congeners, substances other than ethanol in whisky, on the ethanol-induced gastric mucosal damage were examined in the rat model. After the whisky congeners were intragastrically administered previous to or simultaneous with ethanol ingestion, the gastric damage was macroscopically and microscopically measured. The simultaneous administration of the whisky congeners at a dose of 5 mg/kg body weight, which corresponds to the concentration of congeners contained in whisky, with 50% ethanol did not inhibit the hemorrhagic lesions, but inhibited them at a dose of 150 mg/kg. The treatment with the whisky congeners 30 minutes before the ethanol ingestion prevented the ethanol-induced gastric damage in a dose-dependent manner at 0.5 to 150 mg/kg. The butanol extract of the congeners revealed the strongest prevention compared with the ethyl acetate extract or the water fraction. The administration of indomethacin 60 minutes before the congener treatment partly inhibited the protective effects of the congeners, indicating the partial contribution of prostaglandins in this mechanism. The congeners did not prevent the mucosa by action as a "mild irritant" because the immunohistochemical studies using the antimucin monoclonal antibodies showed that no damage was induced by the administration of the congeners. The present results showed that the whisky congeners have a protective activity against ethanol-induced gastric mucosal injury.

Detection and significance of occult metastases in node-negative breast cancer.

The clinical value of lymph node immunohistochemistry was assessed in 343 consecutive patients with apparently node-negative breast cancer using antimucin monoclonal antibodies BC2, BC3 and 3E1.2. Occult metastases were detected in 41 patients (12 per cent). Although most of these were micrometastatic (< 2 mm in diameter), larger or diffuse deposits were found in ten patients. Blind assessment of repeat haematoxylin and eosin stained sections detected metastases in ten of the 41 patients with occult metastases. After a median follow-up of 79 months, patients with occult metastases had a shorter time to disease recurrence (P < 0.05) but not to death. After adjustment for other prognostic factors, the presence of occult metastases in two or more nodes was the most significant predictor of both disease recurrence (P < 0.01) and death (P < 0.01). When the ten patients with positive haematoxylin and eosin sections were excluded from the analysis, the presence of occult metastases in two or more nodes was still associated with a reduced disease-free interval (P < 0.05) and survival (P < 0.05). Lymph node immunohistochemistry is a simple technique affording more accurate definition of nodal involvement than conventional methods.

Molecular pathological subclassification of mucinous adenocarcinoma of the colorectum

The purpose of the present report was to examine the possibility of molecular pathological subtyping of mucinous adenocarcinomas (MAC) of the colorectum. Thirty-five formalin-fixed and paraffin-embedded MAC specimens of the colorectum were analyzed. Genetic alterations of p53 gene and microsatellite instability (MSI) as well as immunohistochemical analysis of mucin subtypes (human gastric mucin (HGM), anti-mucin monoclonal antibody recognizing gastric gland mucous cells-1, MUC2, CD10) and expression levels of human mutL homolog 1 (hMLH1), p53 and Ki-67 were performed. According to MSI and p53 status, these tumors were subclassified into three groups: mutator-type tumors with a high frequency of MSI (20%), suppressor/p53-type tumors with p53 mutation, p53 overexpression or loss of heterozygosity of D17S250 (an adjacent locus to p53; 40%) and the unclassified tumors (40%). The suppressor/p53-type tumors had a significant association with distal colon location (P = 0.019), venous invasion (P = 0.002), extent of lymph node metastasis (P = 0.007) and higher tumor stage (P = 0.018). In contrast, mutator-type tumors had frequent expression of HGM (P = 0.005) and prominent lymphocytic infiltration at the advancing front of the tumor (P = 0.005). These results indicate that MAC of the colorectum could be subclassified according to molecular pathological background, reflecting distinct clinicopathological and phenotypic characteristics.

Appearance of specific mucins recognized by monoclonal antibodies in rat gastric mucosa healing from HCl-induced gastric mucosal damage.

Mucus is an important factor in the physiological defense mechanism of the gastrointestinal tract. We have reported that two distinct antigenicities reacting with anti-mucin monoclonal antibodies (mAbs), HCM31 and RGM26, emerged in epithelial cells regenerating from acetic acid-induced gastric damage in the rat. Here, we examined whether the expression of specific mucins occurred during the healing stage of acute gastric mucosal lesions, and what was the principal alteration of the mucus in the regenerating process of gastric epithelia from slight mucosal lesions. Eight-week-old male Wistar rats were used. The animals were administered 0.6 N hydrochloric acid, or 0.5% carboxymethyl cellulose sodium salt into their stomachs. Twenty-four, 48, and 72 h after the HCl administration, their stomachs were removed. Immunohistochemical observation was performed after staining with the mAbs, RGM21, RGM26, HIK1083, or HCM31. Twenty-four hours after the administration of HCl, mucous cells stained with RGM26 emerged in the deeper area of the surface epithelial cells in the damaged corpus mucosa. After 48 h, HCM31-positive cells were noted in the epithelial cells where the mucosal damage reached more deeply. The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing process from acute gastric mucosal damage.

In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells.

To examine the in vivo effects of macrolide antibiotics on mucus hypersecretion, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats and by intranasal LPS instillation. Oral administration of clarithromycin (CAM) (5-10 mg/kg) significantly inhibited OVA- and LPS-induced mucus production and neutrophil infiltration, whereas josamycin and ampicillin showed no effect. In vitro effects of macrolide antibiotics on airway epithelial cells were examined using NCI-H292 cells and human nasal epithelial cells cultured in air-liquid interface. Mucus secretion was evaluated by ELISA using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18). CAM and erythromycin significantly inhibited spontaneous and tumor necrosis factor-alpha (20 ng/ml)-induced mucus secretion from NCI-H292 cells at 10-6 to 10-7 M and from human nasal epithelial cells at 10-4 to 10-5 M. MUC5AC messenger RNA expression was also significantly inhibited. These results indicate that the 14-member macrolide antibiotics, CAM and erythromycin, exert direct inhibitory effects on mucus secretion from airway epithelial cells and that they may be useful for the treatment of mucus hypersecretion caused by allergic inflammation and LPS stimulation.

Immunohistochemical Localization in Rat Gastrointestinal Tract of a Sialomucin Species Recognized by HCM31, a New Anti-Mucin Monoclonal Antibody

It has been recognized that distinct mucus secreting cells of the gastrointestinal tract express specific type of mucins. We have recently demonstrated that a kind of sialomucin specifically stained with a monoclonal antibody (mAb) HCM31 is temporarily and specifically expressed in the mucous cells regenerated from acetic acid-induced gastric damage in rats. The aim of this study was to immunohistochemically characterize the distribution of the specific type of sialomucins recognized by this mAb throughout the digestive tract and age-dependent alteration of this expression in rats. The gastrointestinal tracts of eight-week-old and eighty-eight-week-old male Sprague Dawley rats were used in this study. In both young and aged rats, HCM31 reacted with the surface mucous cells of the cardiac gland, recognizable as 2 or 3 pits adjacent to the forestomach. The goblet cells in the duodenum, jejunum, ileum, cecum and proximal colon were also stained with HCM31. In the young rat, epithelial cells including the goblet cells in the distal colon and the rectum were not stained with HCM31. On the other hand, the goblet cells in the distal colon and rectum of the aged rats were stained positively with HCM31. These findings indicate that the immunohistochemical observations using this mAb, as well as other anti-mucin mAbs developed by us, should be very useful for the evaluation of changes in the mucin species with respect to the physiological and pathological alterations in the alimentary tract of rats.

Anti-mucin monoclonal antibodies

Anti-mucin monoclonal antibodies

Anti-mucin monoclonal antibodies.

Mucins are of major interest in cell biology, not only are they highly over-expressed in many adenocarcinomas (up to 40-fold increase), but also have important physiological function, and probably more to be determined (1-3). There is much information available on mucins - doubtless because of their unusual structure being heavily glycosylated, but also containing a repeat region rich in the amino acids serine, threonine and proline. This repeat region confers high immunogenicity of the mucins, and as a result, many antibodies (Abs) have been made to mucins of different species (4). Furthermore, the production of Abs led to the cloning of the cDNAs and armed with these reagents (antibodies, cDNA and genomic structures), advances in the knowledge of the structure and function of mucins has been rapid, together with the development of transgenic and gene knockout animals for biological studies (1-9). Here we describe monoclonal antibodies (Mabs) made to the different mucins, including Mucins 1-4, concentrating on human Mucin 1 (MUC1), to variants of MUC1, to regions outside the VNTR of MUC1, mouse Mucin1 (muc1), unusual features and cross reactions of anti-MUC1 Mabs and Abs made by patients in clinical trials. We will especially describe the Mabs produced in our laboratory.