Cancer Antigen 15-3/Mucin 1 Levels in CCTG MA.32: A Breast Cancer Randomized Trial of Metformin vs Placebo.

Background: Circulating levels of cancer antigen (CA) 15-3, a tumor marker and regulator of cellular metabolism, were reduced by metformin in a nonrandomized neoadjuvant study. We examined the effects of metformin (vs placebo) on CA 15-3 in participants of MA.32, a phase III randomized trial in early-stage breast cancer. Methods: A total of 3649 patients with T1-3, N0-3, M0 breast cancer were randomly assigned; pretreatment and 6-month on-treatment fasting plasma were centrally assayed for CA 15-3. Genomic DNA was analyzed for the rs11212617 single nucleotide polymorphism. Absolute and relative change of CA 15-3 (metformin vs placebo) were compared using Wilcoxon rank and t tests. Regression models adjusted for baseline differences and assessed key interactions. All statistical tests were 2-sided. Results: Mean (SD) age was 52.4 (10.0) years. The majority of patients had T2/3, node-positive, hormone receptor-positive, HER2-negative breast cancer treated with (neo)adjuvant chemotherapy and hormone therapy. Mean (SD) baseline CA 15-3 was 17.7 (7.6) and 18.0 (8.1 U/mL). At 6 months, CA 15-3 was statistically significantly reduced in metformin vs placebo arms (absolute geometric mean reduction in CA 15-3 = 7.7% vs 2.0%, P < .001; relative metformin: placebo level of CA 15-3 [adjusted for age, baseline body mass index, and baseline CA 15-3] = 0.94, 95% confidence interval = 0.92 to 0.96). This reduction was independent of tumor characteristics, perioperative systemic therapy, baseline body mass index, insulin, and the single nucleotide polymorphism status (all Ps > .11). Conclusions: Our observation that metformin reduces CA 15-3 by approximately 6% was corroborated in a large placebo-controlled randomized trial. The clinical implications of this reduction in CA 15-3 will be explored in upcoming efficacy analyses of breast cancer outcomes in MA.32.

Role of MUC1 in lubrication of pleural mesothelial cells cultured on fibrine gel.

To elucidate the role of sialomucin in friction reduction, we investigated the sliding friction of pleural mesothelial cells monolayers cultured on fibrine gel. These measurements were performed on normal (4/4 RM-4) and on tumor (CARM-L1 TG3) cell lines. The effect of treatment with neuraminidase, which removes sialic acid from sialomucin, and of dexamethasone, which has shown to increase sialomucin expression, were also assessed. Furthermore, the expression of the main form of cell-surface-associated mucin (MUC1) present in the mesothelium, was assessed by western blot and immunofluorescence, under different experimental conditions. Expression of MUC1 was not significantly different in the two cell lines. Moreover, dexamethasone did not increase the expression of MUC1. Coefficient of kinetic friction (µ) was significantly higher in tumor cells than in normal cells. Neuraminidase increased µ in both cell lines. These results suggest that sialomucin may play a role in reducing the friction of pleural mesothelial cells.

Aberrant MUC1 accumulation in salivary glands of Sjögren's syndrome patients is reversed by TUDCA in vitro.

OBJECTIVES: Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. METHODS: Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-α or IFN-γ and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-κB subunit), TNF-α, IL-1ß, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. RESULTS: MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-α and IFN-γ, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. CONCLUSION: Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.

Dopamine D1 receptor agonists inhibit lung metastasis of breast cancer reducing cancer stemness.

The leading causes of death in breast cancer patients are disease recurrence and metastasis. Growing evidence has suggested that metastasis possibly originates from cancer stem-like cells (CSCs). Previous studies indicated dopamine decreased CSC frequency through activating dopamine D1 receptor pathway. Hence, this study explored the efficacy of two dopamine D1 receptor agonists in lung metastasis of breast cancer and the preliminary mechanism. The two dopamine D1 receptor agonists, fenoldopam (FEN) and l-stepholidine (l-SPD), performed well in decreasing lung metastasis in 4T1 breast cancer model. And the cGMP in the primary tumor was significantly elevated while cAMP mildly elevated in FEN and l-SPD dosing groups. CSC markers (CD44+/CD24- and ALDH+) and MMP2 in 4T1 primary tumor were repressed after dopamine D1 receptor agonist administration while E-cadherin up-regulated. FEN and l-SPD also inhibited cancer stemness and cell motility in vitro, and the inhibitory effects could be reversed by dopamine D1 receptor antagonist SCH23390. Besides, FEN impacted the white blood cell increase caused by breast cancer disease showing decreased neutrophils but increased lymphocytes. Drug safety was verified in aspects of body weight, organ index and tissue section. In conclusion, dopamine D1 receptor agonists FEN and l-SPD showed efficacy in inhibiting metastasis along with good safety in breast cancer, thus providing an alternative for anti-metastasis therapy in the future. Furthermore, this study also indicates that dopamine D1 receptor may be a possible target for metastatic breast cancer treatment and even other cancers at a late stage.

MUC1 Story: Great Expectations, Disappointments and the Renaissance.

In the course of studying human mucin MUC1, the attitude towards this molecule has been changing time and again. Initially, the list of presumable functions of MUC1 was restricted to protecting and lubricating epithelium. To date, it is assumed to play an important role in cell signaling as well as in all stages of oncogenesis, from malignant cell transformation to tumor dissemination. The story of MUC1 is full of hopes and disappointments. However, the scientific interest to MUC1 has never waned, and the more profoundly it has been investigated, the clearer its hidden potential turned to be disclosed. The therapeutic potential of mucin MUC1 has already been noted by various scientific groups at the early stages of research. Over forty years ago, the first insights into MUC1 functions became a strong ground for considering this molecule as potential target for anticancer therapy. Therefore, this direction of research has always been of particular interest and practical importance. More than 200 papers on MUC1 were published in 2016; the majority of them are dedicated to MUC1-related anticancer diagnostics and therapeutics. Here we review the history of MUC1 studies from the very first attempts to reveal its functions to the ongoing renaissance.

Inhibition of MUC1-C regulates metabolism by AKT pathway in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors worldwide. The Mucin 1 (MUC1) heterodimeric protein has been confirmed that is overexpressed in ESCC and induced adverse outcomes. However, the detailed mechanism(s) remained challenging. So, we investigated the relationship between MUC1-C and metabolism in ESCC cells. In the results, TP53-induced glycolysis and apoptosis regulator (TIGAR) was overexpressed and correlative with MUC1-C positively in ESCC tissue. Targeting MUC1-C inhibits AKT-mTORC-S6K1 signaling and blocks TIGAR translation. We found that the inhibitory effect of GO-203 on TIGAR was mediated by inhibition of AKT-mTOR-S6K1 pathway. The findings also demonstrated that the suppressive effect of GO-203 on TIGAR is related to the decrease of glutathione level, the increase of reactive oxygen species and the loss of mitochondrial transmembrane membrane potential. In xenograft tissues, GO-203 inhibited the growth of ESCC cells and lead to the low expression of transmembrane C-terminal subunit (MUC1-C) and TIGAR. This evidence supports the contention that MUC1-C is significant for metabolism in ESCC and indicated that MUC1-C is a potential target for the treatment of ESCC.

Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the Mucin 1 C-terminal subunit (MUC1-C) plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals. Cell lines, primary samples, and xenograft models of CTCL were used to assess synergy of GO-203 with decitabine, a hypomethylating agent. Present studies demonstrate that exposure of CTCL cells to decitabine in combination with GO-203, increased the generation of reactive oxygen species (ROS) levels and decreased levels of scavenger molecules, NADP, NADPH, glutathione, and TIGAR, critical to intracellular redox homeostasis. Dual exposure to GO-203 and decitabine resulted in marked downregulation of DNA methyl transferases demonstrating significant synergy of these agents in inducing global and gene specific hypomethylation. Accordingly, treatment with decitabine and GO-203 upregulated the ROS generating enzymes, NADPH oxidase 4 and dual oxidase 2 potentially due to their effect on epigenomic regulation of these proteins. In concert with these findings, exposure to decitabine and GO-203 resulted in heightened apoptotic death in CTCL cell lines, patient-derived primary samples and in a murine xenograft model. These findings indicate that decitabine intensifies MUC1-C inhibition induced redox imbalance and provides a novel combination of targeted and epigenetic agents for patients with CTCL. Mol Cancer Ther; 16(10); 2304-14. ©2017 AACR.

MUC1-C is a target in lenalidomide resistant multiple myeloma.

Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/ß-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis. We show that the GO-203/LEN combination acts by synergistically increasing ROS and, in turn, suppressing ß-catenin. LEN resistance has been linked to activation of the WNT/ß-catenin→CD44 pathway. In this regard, our results further demonstrate that targeting MUC1-C is effective against LEN-resistant MM cells. Moreover, GO-203 resensitized LEN-resistant MM cells to LEN treatment in association with suppression of ß-catenin and CD44. Targeting MUC1-C also resulted in downregulation of CD44 on the surface of primary MM cells. These findings, and the demonstration that expression of MUC1 and CD44 significantly correlate in microarrays from primary MM cells, provide support for combining GO-203 with LEN in the treatment of MM and in LEN-resistance.

Cigarette Smoke Mediates Nuclear to Cytoplasmic Trafficking of Transcriptional Inhibitor Kaiso through MUC1 and P120-Catenin.

Lung cancer is the leading cause of cancer-related death, and 87% of these deaths are directly attributable to smoking. Using three-dimensional cultures of primary human bronchial epithelial cells, we demonstrated that loss of adherens junction protein, epithelial cadherin, and the aberrant interaction of its adherens junction binding partner, p120-catenin (p120ctn), with the cytoplasmic tail of apical mucin-1 (MUC1-CT) represent initiating steps in the epithelial-to-mesenchymal transition. Smoke provoked the rapid nuclear entry of p120ctn in complex with MUC1-CT that was inhibited using the MUC1-CT inhibitory peptides, PMIP and GO-201. Nuclear entry of p120ctn promoted its interaction with transcriptional repressor kaiso and the rapid shuttling of kaiso to the cytoplasm. Nuclear exit of kaiso permitted the up-regulation of oncogenic transcription factors Fos/phospho-Ser32 Fos, FosB, Fra1/phospho-Ser265 Fra1, which was inhibited through suppression of p120ctn's nuclear export using leptomycin-B. These data indicated that smoke-induced nuclear-to-cytoplasmic translocation of kaiso depends on the nuclear import of p120ctn in complex with MUC1-CT and the nuclear export of kaiso in complex with p120ctn. The presence of MUC1-CT/p120ctn and p120ctn/kaiso complexes in lung squamous cell carcinoma and adenocarcinoma specimens from human patients confirms the clinical relevance of these events. Thus, enhancing kaiso's suppressor role of protumor genes by sequestering kaiso in the nucleus of a smoker's airway epithelium may represent a novel approach of treating lung cancer.

Monoclonal antibody-targeted, temperature-sensitive liposomes: in vivo tumor chemotherapeutics in combination with mild hyperthermia.

The development of actively targeted, responsive delivery vectors holds great promise for cancer therapy. Here, we investigated whether enhanced therapeutic activity of temperature sensitive liposomes (TSL) could be obtained by mild hyperthermia-triggered release of the chemotherapeutic drug doxorubicin (DOX) after hCTMO1 monoclonal antibody (anti-MUC-1) binding and uptake into cancer cells. We showed that traditional TSL (TTSL) liposome systems maintained their physicochemical and thermal properties after conjugation to hCTMO1 full IgG. Receptor-mediated cellular uptake and cytotoxic efficacy of antibody-targeted TTSL (TTSL-Ab) were investigated using 2D and 3D cell culture models. Significant enhancement in cellular uptake and cytotoxic activity after 1h of heating at 42 °C was observed for TTSL-Ab compared to non-targeted liposomes in MUC-1 over-expressing breast cancer cells (MDA-MB-435). Tissue distribution and in vivo therapeutic activity were studied using different heating protocols to explore the effect of mild hyperthermia on the tumor accumulation of targeted TTSL and their therapeutic effect. Application of local, mild hyperthermia (42°C) significantly increased the tumor accumulation of targeted TSL compared to non-targeted liposomes, associated with a moderate improvement in therapeutic activity and survival.

Contact lens care solutions downregulate membrane-associated mucins 1 and 16 in cultured human corneal epithelial cells and at the rat corneal surface in vivo.

OBJECTIVE: The purpose of this study was first to evaluate the effect of multipurpose contact lens care solutions (MPSs) on the expression of membrane-associated mucins (MUC1 and MUC16) in SV40-transformed human corneal epithelial (HCE-T) cells and in vivo rat cornea. The second aim of this study was to determine the role of the common MPS additive boric acid in reducing mucin expression and release. METHODS: The HCE-T cells were exposed to different concentrations of MPS-F, MPS-G, MPS-H, MPS-I, and MPS-J with 100% treatment for 30 minutes and 10% treatment for 24 hours. MUC1 and MUC16 expressions were subsequently analyzed by Western blotting. Wister rats were also subjected to MPS-A, MPS-B, MPS-C, MPS-D, and MPS-E and received phosphate-buffered saline exposure (1 drop in the right eye every 10 minutes for 1 hour). The left eye was used as control. Cornea sections and lysates were used for the immunohistochemical assay of MUC1 and MUC16 expressions. Conditioned media from treated HCE-T cells were also analyzed using Western blotting. RESULTS: The MPSs containing boric acid downregulated MUC1 and MUC16 in the rat cornea, whereas MPSs without boric acid had no effect as demonstrated by the Western blotting and immunohistochemical analysis. Conditioned media from MPS-containing boric acid revealed some trace of MUC16. CONCLUSIONS: The clinical use of MPSs containing boric acid that reduce MUC1 and MUC16 availability should be avoided. Additionally, the presence of MUC16 in the conditioned media suggests that boric acid may have enhanced cleavage of MUC16 at the cell membrane surface.

Monoclonal antibodies therapies for ovarian cancer.

INTRODUCTION: Despite aggressive debulking surgery, intraperitoneal therapies and the use of new drugs for chemotherapy, patients with ovarian cancer (OC) still have poor prognosis and, therefore, new strategies for its management are needed. Molecular-targeted agents can be considered a new option in drug research. Several antigens related to OC have been isolated and they could be potential target of monoclonal antibodies (mAbs); therefore, different mAbs have been developed and are emerging as new potential OC treatments. AREAS COVERED: This article aims to review the literature on the use of mAbs in the treatment of OC. The purposes of this manuscript are to offer a brief explanation of the mechanisms of action of mAbs and to help readers in understanding the current role of mAbs in the treatment of OC. EXPERT OPINION: A deeper knowledge of the molecular biology of OC has brought new developments in targeted therapies. Among these therapies, bevacizumab demonstrated the higher clinical efficacy. Further larger trials are needed to better define the role of the other mAbs in OC treatment. There is a strong need to identify and validate robust biomarkers for a more focused patient selection and for tailoring therapies, optimizing dose and assessing response.

The effect of ethinyl estradiol and drospirenone-containing oral contraceptives upon mucoprotein content of cervical mucus.

OBJECTIVE: To report the effect of oral contraceptives (OC) on cervical mucoprotein content by evaluating quantitatively mucoprotein 1 (MUC1), mucoprotein 2 (MUC2), mucoprotein 5AC (MUC5AC) and mucoprotein 5B (MUC5B) levels. STUDY DESIGN: This prospective controlled study included 20 women of reproductive age who had requested OC. Cervical mucus samples were obtained from the women before use of the OC and after 2 months of OC use. The mucus samples were then evaluated quantitatively for MUC1, MUC2, MUC5AC and MUC5B by ELISA by using specific antibodies. RESULTS: MUC5AC mucoprotein predominated quantitatively both before and after OC use. After OC use, compared to before OC use, variable increases in the levels of all studied mucoproteins were recorded, but the increases in MUC1, MUC2 and MUC5B were statistically significant. The difference in the level of MUC2 was remarkable (+54.36 ± 31.88 ng/mL). CONCLUSION: OC use may change the mucoprotein content (especially for MUC2) of cervical mucus and thus, may cause a highly viscous pattern of cervical mucus which may enhance the contraceptive efficacy of OC pills.

Mucin 1 C-terminal subunit oncoprotein is a target for small-molecule inhibitors.

Mucin 1 (MUC1) is a heterodimeric protein that is overexpressed in diverse human carcinomas. The oncogenic function of the MUC1 C-terminal subunit (MUC1-C) subunit is dependent on the formation of dimers through its cytoplasmic domain; however, it is not known whether MUC1-C can be targeted with small-molecule inhibitors. In the present work, an assay using the MUC1-C cytoplasmic domain (MUC1-CD) was established to screen small-molecule libraries for compounds that block its dimerization. Using this approach, the flavone apigenin was identified as an inhibitor of MUC1-CD dimerization in vitro and in cells. By contrast, the structurally related flavone baicalein was ineffective in blocking the formation of MUC1-CD dimers. In concert with these results, apigenin, and not baicalein, blocked the localization of MUC1-C to the nucleus. MUC1-C activates MUC1 gene expression in an autoinductive loop, and apigenin, but not baicalein, treatment was associated with down-regulation of MUC1 mRNA levels and MUC1-C protein. The results also demonstrate that apigenin-induced suppression of MUC1-C expression is associated with apoptotic cell death and loss of clonogenic survival. These findings represent the first demonstration that the MUC1-C cytoplasmic domain is a target for the development of small-molecule inhibitors.

Oral contraceptive use and salivary C-erbB-2, CEA and CA15-3 in healthy women: a case-control study.

OBJECTIVES: Oral contraceptives (OCP) are highly effective, safe and widely used. Higher exposure to endogenous and exogenous estrogens is generally thought to increase the risk of breast cancer. Therefore, this study was conducted to determine if oral contraceptive use affected the expression of CA 15-3, CEA and C-erb B-2 in the saliva of healthy women. STUDY DESIGN: The participants consisted of 87 healthy women (43 controls and 44 using oral contraceptives) ranging in age from 20 to 54 years. The volunteers participated by giving one - time stimulated whole saliva samples. Then the samples were analysed for CA 15-3, CEA and C-erb B-2 concentrations. RESULTS: The student t-test was used to compare group means for variables with comparable variability. The mean of C-erb B-2, CEA, and CA 15-3 concentrations (in the case and control groups) was (1.93, 1.70), (34.46, 31.62) and (12.58, 16.19) respectively. These differences were not statistically significant. CONCLUSIONS: Our findings suggest that the levels of the cancer biomarkers C-erb B-2, CEA and CA 15-3 were not affected by increased levels of estrogens in the body.

Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer.

The purpose of this study was to investigate the in vitro effect of anti-MUC1 monoclonal antibody (MAb) C595 alone and in combination with docetaxel, on the growth and survival of different epithelial ovarian cancer (EOC) cell lines. MUC1 expression was assessed on EOC cell lines (OVCAR-3, IGROV-1, A2780, CAOV-3, TOV-21G, TOV-112D, SKOV-3 and OV-90) using immunofluorescence labeling and flow cytometry. The effect of MAb C595 alone or in combination with docetaxel on the cell lines was studied by proliferation, colony and TUNEL assays. Our results indicate that all primary and metastatic EOC cell lines tested were positive to MAb C595 (MUC1); MAb C595 inhibited EOC cell proliferation in a MUC1- and dose-dependent manner; low-dose MAb C595 (1/2 of IC50) combined with docetaxel greatly improved efficiency of cell killing in EOC cells and induced apoptosis; the additive effect of MAb C595 was further confirmed in colony forming assays; and cell death following single or combined treatments was associated with the release of cytochrome c and increased caspase-3 activity. These results suggest that MAb C595 used either alone, or combined with docetaxel, is an attractive strategy for targeting human EOC.

Direct targeting of the mucin 1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells.

The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed by approximately 90% of human breast cancers. However, there are no effective agents that directly inhibit MUC1 and induce death of breast cancer cells. We have synthesized a MUC1 inhibitor (called GO-201) that binds to the MUC1 cytoplasmic domain and blocks the formation of MUC1 oligomers in cells. GO-201, and not an altered version, attenuates targeting of MUC1 to the nucleus of human breast cancer cells, disrupts redox balance, and activates the DNA damage response. GO-201 also arrests growth and induces necrotic death. By contrast, the MUC1 inhibitor has no effect on cells null for MUC1 expression or nonmalignant mammary epithelial cells. Administration of GO-201 to nude mice bearing human breast tumor xenografts was associated with loss of tumorigenicity and extensive necrosis, which results in prolonged regression of tumor growth. These findings show that targeting the MUC1 oncoprotein is effective in inducing death of human breast cancer cells in vitro and in tumor models.

Surface Mucin-1 does not play a role in dendritic cell migration.

Mucin-1 (MUC1) is a transmembrane glycoprotein that is upregulated upon maturation of dendritic cells (DC) in vitro or in vivo. One of the proposed functions of surface expressed MUC1 is its involvement in migration of cells. We hypothesized that MUC1 is involved in DC migration since mature DC (mDC) are highly migratory cells and MUC1 is upregulated on the surface of DC upon maturation. In this study we cultured DC using two maturation cocktails, one cocktail containing IL-4, GM-CSF, TNFalpha, PGE2, IL-1 beta and IL-6 (TP1,6-DC) and the other IL-13, GM-CSF, Ribomunyl and IFN-gamma (RI-DC). Both maturation cocktails render DC with a similar surface phenotype including CCR7 expression, but only the former induces a migratory capacity of DC to a CCL19 gradient. To analyze the role of surface-expression of MUC1 on TP1,6-DC, that are capable of migration, expression of MUC1 was prevented by adding an anti-MUC1 antibody (Ab) during the maturation process. Compared with matured DC in the absence of the Ab, no difference was observed in chemokine-induced migratory behaviour between the MUC1+ and MUC1- DC populations in a standard Transwell chemotaxis assay, nor in organotypic cultures. Our data clearly demonstrate that surface MUC1 on DC does not influence intrinsic cell-motility, nor is it involved in cell-cell and cell-matrix dependent migration.