MUC1 in Macrophage: Contributions to Cigarette Smoke–Induced Lung Cancer

Xu, Xiuling; Padilla, Mabel T.; Li, Bilan; Wells, Alexandria; Kato, Kosuke; Tellez, Carmen S.; Belinsky, Steven A.; Kim, Kwang Chul; Lin, Yong

doi:10.1158/0008-5472.can-13-1713

Cited by 21 publications

(28 citation statements)

References 34 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KL-6, a complex carbohydrate antigen of human MUC1, was elevated in AMs and regenerating type 2 pneumocytes in patients with idiopathic interstitial pneumonia (30). A causal effect of cigarette smoke on increased expression of MUC1/Muc1 by mAMs in vivo and human macrophage cell lines was reported (11). The results of the current study are consistent with previous in vivo data demonstrating that Pa lung infection up-regulated mouse Muc1 levels in lung tissue and increased shed Muc1-EC levels in bronchoalveolar lavage fluid (18).…”

Section: Muc1/muc1 Deficiency Enhances Ros Production and Tnf-a Releasupporting

confidence: 92%

“…Moreover, M0 THP-MUC1 shRNA cells had increased TNF-a release in response to Pa compared with M0 THP-control shRNA cells ( Figure 6C). In summary, the collective results of this study indicate that: (1) Increased expression of MUC1 by hAMs has been shown to be associated with the histopathogenesis of some lung diseases (11,30). KL-6, a complex carbohydrate antigen of human MUC1, was elevated in AMs and regenerating type 2 pneumocytes in patients with idiopathic interstitial pneumonia (30).…”

Section: Muc1/muc1 Deficiency Enhances Ros Production and Tnf-a Releamentioning

confidence: 70%

“…MUC1 was originally identified on the apical surfaces of most simple, secretory epithelia (6), and subsequently on a variety of hematopoietic cells, including T and B lymphocytes, dendritic cells, bone marrow mononuclear cells, and macrophages (7)(8)(9)(10)(11). In gastric epithelia, MUC1 contributes to the physicochemical barrier against infectious pathogens (12).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

Kato

Uchino

Lillehoj

et al. 2016

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

MUC1 (MUC in human; Muc in animals) is a transmembrane mucin glycoprotein expressed in mucosal epithelial cells and hematopoietic cells. MUC1 is involved in the resolution of inflammation during airway Pseudomonas aeruginosa (Pa) infection by suppressing Toll-like receptor signaling in airway epithelial cells. Although alveolar macrophages are recognized as critical mediators of cell-mediated immunity against microorganisms inhaled into the airways, the role of MUC1 in regulating their response is unknown. The aims of this study were to determine whether macrophages express MUC1, and, if so, whether MUC1 expression might be associated with macrophage M0/M1/M2 differentiation or phagocytic activity. Human and mouse MUC1/Muc1 expression was drastically up-regulated in classically activated (M1) macrophages compared with nonactivated (M0) and alternatively activated (M2) macrophages. M1 polarization and Pa stimulation each increased MUC1 ectodomain shedding from the macrophage surface in a TNF-a-converting enzyme-dependent manner. MUC1/Muc1 deficiency in M0 macrophages increased adhesion and phagocytosis of Pa and Escherichia coli compared with MUC1/Muc1-expressing cells, and attenuation of phagocytosis by MUC1 was augmented after polarization into M1 macrophages compared with M0 macrophages. Finally, MUC1/Muc1 deficiency in macrophages increased reactive oxygen species production and TNF-a release in response to Pa compared with MUC1/Muc1-sufficient cells. These results indicate that MUC1/Muc1 expression by macrophages is predominantly in the M1 subtype, and that MUC1/Muc1 expression in these cells decreases their phagocytic activity in an antiinflammatory manner.

show abstract

Section: Muc1/muc1 Deficiency Enhances Ros Production and Tnf-a Releasupporting

confidence: 92%

Section: Muc1/muc1 Deficiency Enhances Ros Production and Tnf-a Releamentioning

confidence: 70%

mentioning

confidence: 99%

See 1 more Smart Citation

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

Kato

Uchino

Lillehoj

et al. 2016

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Two micrograms of RNA were used as a template for cDNA synthesis with a reverse transcription kit (Promega). An equal volume of cDNA product was subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis according to our previous study (21). The following primers were used in the PCR reactions: MUC1, forward primer 5′-ACAATTGACTCTGGCCTTCCG-3′ and reverse primer 5′-TGGG TTTGT GTA AG AGAGGCT-3′; β-actin, forward primer: 5′-CCA GCCTTCCTTCCTGGGCAT-3′ and reverse primer 5′-AGGAGCAATGATCT TGATCTTCATT-3′; Catalase, forward primer 5′-GGGAGAAGGCAAATCT GTGA-3′ and reverse primer 5′-GCACA TCTA GCAC AGGA GAAT-3′.…”

Section: Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

“…We recently found that chronic cigarette smoke exposure induces persistent MUC1 overexpression in human lung bronchial epithelial cells, which facilitates cigarette smoke-induced cell transformation through EGFR-mediated cell survival signaling (20). In addition, MUC1 mediates cigarette smoke extract-induced TNFα secretion from macrophages to engender a lung cancer-prone microenvironment (21), suggesting that MUC1 functions in both lung macrophages and bronchial epithelial cells for lung cancer development. However, direct evidence for the role and mechanisms of MUC1 in acquired chemoresistance in lung cancer is lacking.…”

Section: Introductionmentioning

confidence: 99%

A signaling pathway consisting of miR-551b, catalase and MUC1 contributes to acquired apoptosis resistance and chemoresistance

Xu¹,

Wells²,

Padilla³

et al. 2014

Carcinogenesis

Self Cite

View full text Add to dashboard Cite

Acquired chemoresistance is a major challenge in cancer therapy. While the oncoprotein Mucin-1 (MUC1) performs multiple roles in the development of diverse human tumors, whether MUC1 is involved in acquired chemoresistance has not been determined. Using an acquired chemoresistance lung cancer cell model, we show that MUC1 expression was substantially increased in cells with acquired apoptosis resistance (AR). Knockdown of MUC1 expression effectively increased the sensitivity of these cells to the apoptotic cytotoxicity of anticancer therapeutics, suggesting that MUC1 contributes to acquired chemoresistance. Decreased catalase expression and increased cellular reactive oxygen species (ROS) accumulation were found to be associated with MUC1 overexpression. Scavenging ROS with butylated hydroxyanisole or supplying exogenous catalase dramatically suppressed MUC1 expression through destabilizing MUC1 protein, suggesting that reduced catalase expression mediated ROS accumulation is accounted for MUC1 overexpression. Further, we found that increased miR-551b expression in the AR cells inhibited the expression of catalase and potentiated ROS accumulation and MUC1 expression. Finally, by manipulating MUC1 expression, we found that MUC1 promotes EGFR-mediated activation of the cell survival cascade involving Akt/c-FLIP/COX-2 in order to protect cancer cells from responding to anticancer agents. Thus, our results establish a pathway consisting of miR-551b/catalase/ ROS that results in MUC1 overexpression, and intervention against this pathway could be exploited to overcome acquired chemoresistance.

show abstract

The Microenvironment of Lung Cancer and Therapeutic Implications

Mittal

Rayes

Narula

et al. 2015

Advances in Experimental Medicine and Biology

113

View full text Add to dashboard Cite

The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetically stable intratumoral stromal cells result in an "activated/reprogramed" stroma that promotes carcinogenesis by contributing to inflammation, immune suppression, therapeutic resistance, and generating premetastatic niches that support the initiation and establishment of distant metastasis. The lungs present a unique milieu in which tumors progress in collusion with the TME, as evidenced by regions of aberrant angiogenesis, acidosis and hypoxia. Inflammation plays an important role in the pathogenesis of lung cancer, and pulmonary disorders in lung cancer patients such as chronic obstructive pulmonary disease (COPD) and emphysema, constitute comorbid conditions and are independent risk factors for lung cancer. The TME also contributes to immune suppression, induces epithelial-to-mesenchymal transition (EMT) and diminishes efficacy of chemotherapies. Thus, the TME has begun to emerge as the "Achilles heel" of the disease, and constitutes an attractive target for anti-cancer therapy. Drugs targeting the components of the TME are making their way into clinical trials. Here, we will focus on recent advances and emerging concepts regarding the intriguing role of the TME in lung cancer progression, and discuss future directions in the context of novel diagnostic and therapeutic opportunities.

show abstract

MUC1 in Macrophage: Contributions to Cigarette Smoke–Induced Lung Cancer

Cited by 21 publications

References 34 publications

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

A signaling pathway consisting of miR-551b, catalase and MUC1 contributes to acquired apoptosis resistance and chemoresistance

The Microenvironment of Lung Cancer and Therapeutic Implications

Contact Info

Product

Resources

About