Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens

Zhang, Shengle; Zhang, Helen S.; Cordon‐Cardo, Carlos; Reuter, Victor E.; Singhal, Anil; Lloyd, Kenneth O.; Livingston, Philip O.

doi:10.1002/(sici)1097-0215(19970926)73:1<50::aid-ijc9>3.0.co;2-0

Cited by 215 publications

(58 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biemer-Huttmann et al demonstrated MUC4 expression in 34% of adenocarcinomas and 47% of mucinous colon cancers and suggested an inverse association between MUC4 expression and tumor stage in MUC4-positive tissues [30]. Similarly, Zhang et al observed intense MUC4 expression in 50% of colon cancers [31]. The findings of the present study align with Shanmugam et al [27] which demonstrated strong MUC4 expression in normal colon with progressive decrease during progression to carcinoma.…”

Section: Discussionsupporting

confidence: 88%

Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

et al. 2016

View full text Add to dashboard Cite

Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in prevention of colorectal cancer. Recent evidences advocate the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma-carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed that MUC2, MUC4 expression were downregulated (p<0.0001) and MUC1, MUC5AC expression were upregulated (p=0.01) during adenoma-adenocarcinoma progression. Expression of MUC17 was downregulated in inflamed tissues compared to normal tissues, but its increased expression differentiated adenomas (p=0.0028) and adenocarcinomas (p=0.025) from inflammation. MUC1 specific glycan-Tn/STn-MUC1 showed higher expression in hyperplastic polyps (p=0.023), adenomas (p=0.042) and adenocarcinomas (p=0.0096) compared to normal. Multivariate regression analyses indicated that a combination of MUC2, MUC5AC, and MUC17 could effectively discriminate adenoma-adenocarcinoma from hyperplastic polyps. Altogether, a combined analysis of altered mucins and mucin-associated glycans is a useful approach to distinguish premalignant/malignant lesions of colon from benign polyps.

show abstract

Section: Discussionsupporting

confidence: 88%

Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Zhang et al looked at the normal tissue expression of Le Y using BR96 antibody to better understand its regulation compared with cancers [198]. The following normal tissues expressed Le Y : spleen and epithelial cells from the lung, breast, prostate, colon, stomach, pancreas, uterus, and ovary, the esophagus, testes, tonsils, salivary glands, and the Paneth cells of the small intestinal epithelium [197].…”

Section: The Blood Group Lewis Related Tumor-associated Antigensmentioning

confidence: 99%

Cancer vaccines and carbohydrate epitopes

Heimburg-Molinaro

Lum

Vijay

et al. 2011

Vaccine

217

152

View full text Add to dashboard Cite

Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related LewisY, Sialyl LewisX and Sialyl LewisA, and LewisX, (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.

show abstract

“…FUT4 catalyzes the transfer of the Fuc of GDP-Fuc to the N-acetylglucosamine of the sugar chain, and FUT4 is a key enzyme in the synthesis of the tumor-associated carbohydrate antigen LeY. Recent studies and our previous work revealed that FUT4/LeY was highly expressed in a variety of solid tumors including breast cancer, ovarian cancer, pancreatic cancer, colon cancer, melanoma and NSCLC and was associated with invasion, metastasis, and poor prognosis [14–18]. Our recent study also showed that FUT4/LeY could activate epidermal growth factor receptor (EGFR) and promote the EMT, invasion, and metastasis of NSCLC through mitogen-activated protein kinase (MAPK)/NF-κB pathway [19].…”

Section: Introductionmentioning

confidence: 99%

Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation

Wang

Zhang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-β1(TGF-β1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY- mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.

show abstract

Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens

Cited by 215 publications

References 20 publications

Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

Cancer vaccines and carbohydrate epitopes

Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation

Contact Info

Product

Resources

About