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Biomedical subjects

James C Byrd

Publications and source records attributed to James C Byrd.

18 recordsLinked to original sources
PubMed2006

Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa.

BACKGROUND: Calcium and vitamin D are chemopreventive agents for colorectal neoplasia. Studies of the effects of calcium and vitamin D on early surrogate markers of reduced risk, such as proliferation, have been limited to evaluation of the flat colorectal mucosa. Biologic changes that may occur in colorectal adenomas after chemopreventive regimens have not been reported. METHODS: In the current study, adenomatous polyps were transected, approximately 50% were removed for histologic examination, and the remnants tattooed before the administration of either calcium carbonate (1500 mg 3 times daily) plus vitamin D(3) 400 IU or a placebo for 6 months. At study end, polyp remnants were resected completely and were used for histologic examination. Immunohistochemical staining was performed in both flat mucosa and in polyp tissue. Proliferation was assessed by MIB-1 staining; apoptosis was assessed by terminal deoxyuridine triphosphate-biotin nick-end labeling, BAK, and Bcl-2 staining; and cytokeratin AE1, vitamin D receptor, MUC5AC mucin, and galectin-3 were assessed by immunohistochemistry. RESULTS: Nineteen patients, including 11 patients in the treatment group and 8 patients in the control group, completed the study. Proliferative indices fell both in flat mucosa and in polyps in the treatment group, and there were no significant changes in the control group. Apoptosis and Bcl-2 immunostaining were unchanged in both groups, but the frequency of BAK-immunostained cells in the interior of polyps rose significantly. Vitamin D receptor staining increased slightly and significantly in flat rectal tissue in the treatment group. There were no significant changes in galectin-3 staining, but a striking reduction in MUC5AC mucin staining in polyps was observed after treatment with calcium plus vitamin D. CONCLUSIONS: The administration of a calcium plus vitamin D chemopreventive regimen resulted in several changes in adenomatous tissue that may have contributed to reduced polyp formation.

Adenoma↗
PubMed2006

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma.

BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma. METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0-6), and 1.5 (0-9) respectively. CONCLUSION: A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.

Journal Article↗
PubMed2006

Magnetic resonance imaging evaluation of patellofemoral malalignment.

PURPOSE: The purpose of this study was to determine the relationship between anterior knee pain secondary to suspected patellofemoral malalignment and tibial tubercle lateralization, patellar tilt, and patellar lateralization on magnetic resonance imaging. METHODS: We compared the bony relationships of the knee in patients with anterior knee pain and patients with nonspecific internal derangements of the knee. We measured the lateral deviation of the tibial tubercle and the patella from the trochlea, patellar tilt, and patellar and patellar tendon length. RESULTS: The symptomatic knees of patients with anterior knee pain had significantly (P < or = .01) greater lateralization of the tibial tubercle and lateral patellar tilt than did knees of the control group. Patella alta appears to be more common in subjects with anterior knee pain. CONCLUSIONS: Magnetic resonance imaging determination of tibial tubercle lateralization and patellar tilt correlates positively with the clinical diagnosis of anterior knee pain, suggesting that patellofemoral pain is caused by subtle malalignment. LEVEL OF EVIDENCE: Level III, development of diagnostic criteria on basis of nonconsecutive patients.

Adult↗
PubMed2005

Phosphorylation of galectin-3 contributes to malignant transformation of human epithelial cells via modulation of unique sets of genes.

Galectin-3 is a multifunctional beta-galactoside-binding protein implicated in apoptosis, malignant transformation, and tumor progression. The mechanisms by which galectin-3 contributes to malignant progression are not fully understood. In this study, we found that the introduction of wild-type galectin-3 into nontumorigenic, galectin-3-null BT549 human breast epithelial cells conferred tumorigenicity and metastatic potential in nude mice, and that galectin-3 expressed by the cells was phosphorylated. In contrast, BT549 cells expressing galectin-3 incapable of being phosphorylated (Ser6-->Glu Ser6-->Ala) were nontumorigenic. A microarray analysis of 10,000 human genes, comparing BT549 transfectants expressing wild-type and those expressing phosphomutant galectin-3, identified 188 genes that were differentially expressed (>2.5-fold). Genes affected by introduction of wild-type phosphorylated but not phosphomutant galectin-3 included those involved in oxidative stress, a novel noncaspase lysosomal apoptotic pathway, cell cycle regulation, transcriptional activation, cytoskeleton remodeling, cell adhesion, and tumor invasion. The reliability of the microarray data was validated by real-time reverse transcription-PCR (RT-PCR) and by Western blot analysis, and clinical relevance was evaluated by real-time RT-PCR screening of a panel of matched pairs of breast tumors. Differentially regulated genes in breast cancers that are also predicted to be associated with phospho-galectin-3 in transformed BT549 cells include C-type lectin 2, insulin-like growth factor-binding protein 5, cathepsins L2, and cyclin D1. These data show the functional diversity of galectin-3 and suggest that phosphorylation of the protein is necessary for regulation (directly or indirectly) of unique sets of genes that play a role in malignant transformation.

Animals↗
PubMed2005

Bile acids induce MUC2 overexpression in human colon carcinoma cells.

BACKGROUND: Mucin alterations are a common feature of colonic neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the colon. Bile acids have been linked to colorectal carcinogenesis and mucin secretion, but their effects on mucin gene expression in human colon carcinoma cells is unknown METHODS: Human colon carcinoma cells were treated </= 6 hours with 10-200 microM deoxycholate, chenodeoxycholate, or ursodeoxycholate. MUC2 protein was assayed by Western blot analysis and MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct. Transcription activator protein 1 (AP-1) activity was measured using an AP-1 reporter construct and confirmed by Western blot analysis for c-Jun/AP-1. RESULTS: MUC2 transcription and MUC2 protein expression were increased three to fourfold by bile acids in a time and dose-dependent manner with no effect on cell viability. AP-1 activity was also increased (deoxycholate > chenodeoxycholate > ursodeoxycholate). Treatment with the putative chemopreventive agent curcumin, which decreased AP-1 activity, also decreased MUC2 transcription. Cotransfection with a dominant negative AP-1 vector decreased MUC2 transcription, confirming the significance of AP-1 in MUC2 induction by deoxycholate. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid-induced MUC2 transcription and AP-1 activity, whereas inhibitors of MAP kinase had no effect. CONCLUSIONS: Bile acids induced mucin expression in human colon carcinoma cells by increasing MUC2 transcription through a process involving MAP kinase-independent, PKC-dependent activation of AP-1.

Antineoplastic Agents↗
PubMed2005

Domain interactions of the mannose 6-phosphate/insulin-like growth factor II receptor.

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) forms oligomeric structures important for optimal function in binding and internalization of Man-6-P-bearing extracellular ligands as well as lysosomal biogenesis and growth regulation. However, neither the mechanism of inter-receptor interaction nor the dimerization domain has yet been identified. We hypothesized that areas near the ligand binding domains of the receptor would contribute preferentially to oligomerization. Two panels of minireceptors were constructed that involved truncations of either the N- or C-terminal regions of the M6P/IGF2R encompassing deletions of various ligand binding domains. alpha-FLAG or alpha-Myc-based immunoprecipitation assays showed that all of the minireceptors tested were able to associate with a full-length, Myc-tagged M6P/IGF2R (WT-M). In the alpha-FLAG but not alpha-Myc immunoprecipitation assays, the degree of association of a series of C-terminally truncated minireceptors with WT-M showed a positive trend with length of the minireceptor. In contrast, length did not seem to affect the association of the N-terminally truncated minireceptors with WT-M, except that the 12th extracytoplasmic repeat appeared exceptionally important in dimerization in the alpha-FLAG assays. The presence of mutations in the ligand-binding sites of the minireceptors had no effect on their ability to associate with WT-M. Thus, association within the heterodimers was not dependent on the presence of functional ligand binding domains. Heterodimers formed between WT-M and the minireceptors demonstrated high affinity IGF-II and Man-6-P-ligand binding, suggesting a functional association. We conclude that there is no finite M6P/IGF2R dimerization domain, but rather that interactions between dimer partners occur all along the extracytoplasmic region of the receptor.

Binding Sites↗
PubMed2005

Galectin-3 modulates MUC2 mucin expression in human colon cancer cells at the level of transcription via AP-1 activation.

BACKGROUND & AIMS: Galectin-3 and MUC2 intestinal mucin each have been correlated with the malignant behavior of colon cancer cells. Galectin-3 modulates expression of MUC2 protein, but the specific regulatory mechanisms are unknown. This study sought to determine how galectin-3 increases MUC2 expression. METHODS: Galectin-3 levels in human colon cancer cells of high and low metastatic ability were manipulated via expression of galectin-3 complementary DNA in sense or antisense orientation. Galectin-3 and MUC2 protein expression were determined by Western analysis and immunocytochemistry. Transient transfections of promoter reporter constructs were used to monitor MUC2 transcription and AP-1 activity. Electrophoretic mobility shift assays, site-directed mutagenesis, and chromatin immunoprecipitation were used to monitor the participation of AP-1 in MUC2 transcription. RESULTS: Alterations in galectin-3 levels correlated with both MUC2 protein expression and transcription. By using MUC2 promoter constructs of different lengths, galectin-3 responsiveness was found between 1500 and 2186 bp upstream of the translation start site, a region that contains 1 consensus AP-1 binding site. AP-1 activity paralleled MUC2 transcription in the different cell lines. Mutation in the AP-1 site markedly decreased MUC2 promoter activity, and MUC2 transcription was inhibited by cotransfection with a dominant-negative AP-1 vector. Electrophoretic mobility shift assays, co-immunoprecipitation, and chromatin immunoprecipitation analyses suggested an association between galectin-3, c-Jun, and Fra-1 in forming a complex at the AP-1 site on the MUC2 promoter. CONCLUSIONS: Galectin-3 up-regulation of MUC2 transcription occurs at the level of transcription through AP-1 activation. This may have important implications for understanding the role of galectin-3 and MUC2 in colon cancer metastasis.

Cell Line, Tumor↗
PubMed2004

Alternative splicing of the human MUC2 gene.

Human colon cancers differ in amounts of MUC2 mucin synthesized. However, it is unclear whether MUC2 encodes a single protein. When clones of human colon cancer cells were assayed with antibodies against the TR2 mucin repeat or non-TR2 epitopes, differences in relative expression of MUC2 proteins suggested multiple immunoreactive forms. RT-PCR analysis detected the established 15kbp MUC2 cDNA and a novel form (designated MUC2.1) lacking the MUC2 TR2 repeat. Sequencing of cDNA and genomic DNA indicated that MUC2.1 results from an alternate splice donor. RT-PCR with splice-junction spanning primers confirmed the expression of MUC2.1 mRNA. Anti-MUC2.1 antibody stained colon cancer cells and normal colon in a pattern different from TR2-specific antibody. The presence of MUC2.1 mucin may help us to explain previous conflicting reports that have attempted to correlate the relative abundance of MUC2 protein and/or mRNA with the biological behavior of colon cancer cells.

Alternative Splicing↗
PubMed2004

A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer.

BACKGROUND & AIMS: Galectin-3 is a beta-galactoside-binding protein implicated in tumor progression and metastasis of colorectal cancers. To determine whether circulating galectin-3 ligands are related to the presence of colon cancer, we sought to identify and quantify ligands in serum that bind to galectin-3. METHODS: Sera from patients with colon cancer, adenomas, and normal individuals were desialylated, reduced, and separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and blots probed with biotinylated galectin-3. RESULTS: In colon cancer sera, the major galectin-3 ligand was a 40-kilodalton band distinct from mucin, carcinoembryonic antigen, and Mac-2 binding protein. Serum 40-kilodalton ligand was 10- to 30-fold higher in patients with colon cancer than in healthy subjects. Ligand was purified by gel filtration, affinity precipitation on galectin-3/agarose, and SDS-PAGE. When tryptic peptides were analyzed by matrix-assisted laser-desorption ionization mass spectrometry and protein database searching, the 40-kilodalton ligand was identified as haptoglobin beta subunit. In confirmation of this finding, depletion of haptoglobin by immunoprecipitation also eliminated the 40-kilodalton ligand. Colon cancer sera had only a modest increase in total haptoglobin as compared with healthy subjects, suggesting that the structure rather than the amount of haptoglobin is altered in patients with colon cancer. Immunohistochemical staining confirmed the absence of haptoglobin in normal colon and the ectopic expression of haptoglobin in colon cancers and adenomatous polyps. CONCLUSIONS: A major circulating ligand for galectin-3, which is elevated in the sera of patients with colon cancer, is a cancer-associated glycoform of haptoglobin.

Adenoma↗
PubMed2004

Literacy and numeracy skills and anticoagulation control.

BACKGROUND: The ability to use printed material to function in society (literacy) and to handle basic numerical concepts (numeracy) may have implications in patients' ability to follow dosing schedules. We examined literacy and numeracy skills among patients on warfarin and explored their association with anticoagulation control. METHODS AND RESULTS: Patients older than 50 years attending two anticoagulation management units were prospectively enrolled. We measured literacy, numeracy, and international normalized ratio (INR). During a 3-month follow-up period, we calculated the variability of the INR and the amount of time a patient's INR was within his or her therapeutic range, variables associated with bleeding and effectiveness. Among 143 patients, only 75 (52.4%) were able to read health-related words at the eighth grade level or less. Patients' self-reported grade completed was higher than the measured literacy grade level (kappa = 0.21). While 79.0% had completed at least eight grades, only 47.6% had a score at that grade level. Sixty-nine patients answered none or correctly answered fewer than two of the six numeracy questions (48.3%). The INR variability was higher among patients with lower literacy (P = 0.009) and lower numeracy skills (P = 0.004). The time in range was similar among patients at different literacy levels (P = 0.9). Patients with lower numeracy level spent more time above their therapeutic range (P = 0.04) and had a trend of less time spent in range (P = 0.10). CONCLUSIONS: Low literacy was prevalent among study patients taking warfarin. Low literacy and numeracy were associated with measures of poor anticoagulation control.

Aged↗
PubMed2003

Binding of urokinase-type plasminogen activator receptor (uPAR) to the mannose 6-phosphate/insulin-like growth factor II receptor: contrasting interactions of full-length and soluble forms of uPAR.

Urokinase-type plasminogen activator receptor (uPAR) binding by the mannose 6-phosphate/insulin-like growth factor II receptor (Man-6-P/IGF2R) is considered important to Man-6-P/IGF2R tumor suppressor function via regulation of cell surface proteolytic activity. Our goal was to map the uPAR binding site of the Man-6-P/IGF2R by analyzing the uPAR binding characteristics of a panel of minireceptors containing different regions of the Man-6-P/IGF2R extracytoplasmic domain. Coimmunoprecipitation assays revealed that soluble recombinant uPAR (suPAR) bound the Man-6-P/IGF2R at two distinct sites, one localized to the amino-terminal end of the Man-6-P/IGF2R extracytoplasmic domain (repeats 1-3) and the other to the more carboxyl-terminal end (repeats 7-9). These sites correspond with the positions of the two Man-6-P binding domains of Man-6-P/IGF2R. Indeed, the suPAR-Man-6-P/IGF2R interaction was inhibited by Man-6-P, and binding-competent su-PAR species represented a minor percentage (8-30%) of the suPAR present. In contrast, Man-6-P/IGF2R binding of endogenous, full-length uPAR solubilized from plasma membranes of the prostate cancer cell line, PC-3, was not inhibited by Man-6-P. Further studies showed that very little (<5%) endogenous uPAR was Man-6-P/IGF2R binding-competent. We conclude that, contrary to previous reports, the interaction between uPAR and Man-6-P/IGF2R is a low percentage binding event and that suPAR and full-length uPAR bind the Man-6-P/IGF2R by different mechanisms.

Animals↗
PubMed2003

Opposing roles for the insulin-like growth factor (IGF)-II and mannose 6-phosphate (Man-6-P) binding activities of the IGF-II/Man-6-P receptor in the growth of prostate cancer cells.

The IGF-II/mannose 6-phosphate (Man-6-P) receptor (IGF2R) binds IGF-II and Man-6-P-bearing ligands at distinct binding sites. Analysis of IGF2R expression and function suggested that decreased IGF2R expression could partly account for the increased growth of lymph node carcinoma of the prostate (LNCaP) human prostate cancer cells observed with increasing passage in culture. However, LNCaP cells that expressed a Myc-tagged IGF2R (IGF2RMyc) proliferated more rapidly than control cells transfected with the empty vector. LNCaP cells expressing a mutant IGF2R incompetent to bind IGF-II (IGF2RMyc I/T) proliferated more rapidly than both vector-transfected cells and cells expressing the IGF2RMyc. In contrast, forced expression of IGF2RMyc in PC-3 human prostate cancer cells resulted in decreased proliferation, compared with control cells. As in LNCaP cells, PC-3 cells expressing IGF2RMyc I/T proliferated more rapidly than vector-transfected cells. The subcellular distribution and ability to internalize cell-surface IGF-II of IGF2RMyc were indistinguishable from endogenous IGF2R in PC-3 cells. These data suggest that the IGF-II- and Man-6-P-binding functions of the IGF2R have opposing activities, with respect to growth of prostate cancer cells. The magnitude of each activity in a given cell type seems to determine whether the net effect of the IGF2R on cell growth is inhibitory or stimulatory.

Cell Division↗
PubMed2003

The insulin-like growth factor II/mannose 6-phosphate receptor: implications for IGF action in breast cancer.

The insulin-like growth factors, particularly IGF-II, interact with multiple cell surface receptors. One of these receptors, the insulin-like growth factor II/mannose 6-phosphate receptor (IGF2R, also called the Type II IGF receptor), has a structure distinct from IGF1R or the insulin receptor. While IGF2R binds IGF-II with high affinity, it also serves as a cell surface receptor for many other proteins relevant to breast cancer biology. As such, IGF2R could play a role in several different key cellular functions including IGF-II action, lysosome biogenesis, and regulation of several novel ligands. These possibilities, along with the intriguing demonstration of loss of heterozygosity at the IGF2R locus, provide clues that this receptor could have an important function in breast cancer. This review will discuss potential ways that IGF2R could influence breast cancer biology.

Journal Article↗
PubMed2002

Chronic ethanol administration decreases the ligand binding properties and the cellular content of the mannose 6-phosphate/insulin-like growth factor II receptor in rat hepatocytes.

We have shown previously that chronic ethanol administration impairs the maturation of lysosomal enzymes in rat hepatocytes. The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR) is a protein that facilitates the transport of lysosomal enzymes into the lysosome. Therefore, we examined whether ethanol consumption altered the ligand binding properties and the cellular content of M6P/IGF-IIR. Rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric maltose-dextrin for either 1 week or 5-7 weeks. Hepatocytes prepared from these animals were examined for receptor-ligand binding and receptor content. One week of ethanol feeding had no significant effect on ligand [radioiodinated pentamannose phosphate conjugated to bovine serum albumin ((125)I-PMP-BSA)] binding to hepatocytes, but cells from rats fed ethanol for 5-7 weeks bound less (125)I-PMP-BSA than pair-fed controls. Scatchard plot analysis revealed that the number of (125)I-PMP-BSA binding sites in hepatocytes from ethanol-fed rats was 49% lower than that of controls. (125)I-PMP-BSA binding by perivenular (PV) and periportal (PP) hepatocytes from ethanol-fed rats was, respectively, 40 and 48% lower than their controls, but there was no significant difference between these two types of hepatocytes. Ligand blot analysis using (125)I-insulin-like growth factor II ((125)I-IGF-II) also showed that the receptor in lysates of hepatocytes from ethanol-fed rats bound 26-27% less ligand than controls. Similarly, immunoblot analysis of cell lysates from ethanol-fed rats revealed 62% lower levels of immunoreactive M6P/IGF-IIR than controls. Feeding rats a low carbohydrate-ethanol diet did not exacerbate the reduction in M6P/IGF-IIR-ligand binding nor did it reduce the levels of immunoreactive receptor. Our findings indicate that chronic ethanol consumption lowers M6P/IGF-IIR activity and content in hepatocytes. This reduction may account, in part, for the impaired processing and delivery of acid hydrolases to lysosomes previously observed in ethanol-fed rats.

Animals↗
PubMed2002

Expression of human intestinal mucin is modulated by the beta-galactoside binding protein galectin-3 in colon cancer.

BACKGROUND & AIMS: Alterations in the production of the beta-galactoside binding protein galectin-3 and of MUC2 intestinal mucin have been independently correlated with the malignant behavior of human colon cancer cells. MUC2 mucin is a major ligand for galectin-3, and colon cancer cells that differ quantitatively in MUC2 expression may also vary in expression of galectin-3. The current study was designed to investigate the relationship between galectin-3 production and MUC2 mucin synthesis by human colon cancer cells. METHODS: The effect of galectin-3 on MUC2 mucin production was assessed by stable transfection of sense and antisense galectin-3 expression constructs under the control of constitutive or tetracycline-inducible promoters into human colon cancer cells. Galectin-3 and MUC2 expression were determined by fluorescence-activated cell sorter (cell surface galectin-3), Western and Northern analysis (galectin-3, MUC2), and gel filtration of secreted high-weight glycoprotein (MUC2). In vitro results were confirmed in vivo by analysis of cecal xenografts in athymic mice. RESULTS: Colon cancer cells with high levels of galectin-3 also had high levels of MUC2 mucin, whereas those with low galectin-3 levels had low MUC2 levels. Alterations in galectin-3 levels by expression of sense or antisense galectin-3 constructs resulted in parallel alterations of MUC2 protein and RNA. Induction of antisense to galectin-3 in vivo was associated with decreases in both galectin-3 and MUC2 protein in cecal xenografts. CONCLUSIONS: The beta-galactoside binding protein galectin-3 modulates the expression of its major ligand MUC2 mucin in human colon cancer cells. This may have important implications for understanding the role of galectin-3 in colon cancer metastasis.

Animals↗
PubMedDate not supplied

Mucins and mucin binding proteins in colorectal cancer.

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.

Adenocarcinoma↗