Implications on glycobiological aspects of tumor hypoxia in breast ductal carcinoma in situ

Rêgo, Moacyr Jesus Barreto de Melo; Mello, Gabriela Souto Vieira de; Santos, Carlos André da Silva; Chammas, Roger; Beltrão, Eduardo Isidoro Carneiro

doi:10.1007/s00795-013-0013-4

Cited by 14 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also observed that Gal-1 expression was found mainly in the extracellular matrix and tumor-associated stromal cells, demonstrating their importance in the relationship between a tumor and its microenvironment [226, 227]. …”

Section: Hypoxia Alters Cell Location Of Galectins and Interaction Wimentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

show abstract

Section: Hypoxia Alters Cell Location Of Galectins and Interaction Wimentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…This carefully orchestrated modulation of glycan diversity during development implies corresponding and important functions for these molecules (1,12). There is evidence that glycan structures reflect their evolutionary backgrounds and functional aspects in various contexts, including differentiation, development, fertilization, inflammation, cell adhesion, and cell-cell recognition (13).…”

Section: Introductionmentioning

confidence: 99%

Glycomic profile of the human parotid gland between 18th and 26th week of fetal development

Rego¹,

Filho²,

Sobral

et al. 2016

J Oral Sci

View full text Add to dashboard Cite

The formation of new and functional structural components of several organs, such as parotid glands, can be influenced by the glycocode. This study analyzed the glycobiology of parotid salivary gland tissue during fetal development using specific biochemical probes (lectins and antibodies). Eleven parotid gland samples from human fetuses were obtained from spontaneous abortions at 14-28 weeks of gestation, and tissue sections were analyzed for lectin histochemistry and immunohistochemistry. From the 18th to 26th week, Canavalia ensiformis agglutinin, wheat germ agglutinin, Ulex europaeus agglutinin-I, peanut agglutinin, Sambucus nigra agglutinin, and Vicia villosa agglutinin lectin staining were predominantly observed in the apical and/or basement membranes of the ducts and tubulo-acinar units. Moreover, the presence of galectin-1 was found in the membrane, cytoplasm, and nucleus of both structures. Conversely, Gal-3 and mucin-1 were restricted to the glandular ducts. The lectin staining pattern changed during the weeks evaluated. Nevertheless, the carbohydrate subcellular localization represented a key factor in the investigation of structural distribution profiles and possible roles of these glycans in initial parotid gland development.

show abstract

“…In some specific environments, such as necrotic areas, Gal-3 and its ligands are overexpressed in glioblastoma in hypoxic regions known as pseudopalisades [39], as well as in regions around necrotic areas from ductal carcinoma in situ of the breast, as demonstrated in a previous study by our group [12]. Another interesting result was the low immunopositivity of staining with M338 antibody which recognizes N-terminal region of Gal-3, a fact which could be relate to N-terminal cleavage performed by matrix metalloproteinases, as well as phosphorylation in hypoxic regions [40,41].…”

Section: Discussionmentioning

confidence: 90%

“…The excess reagent was removed in two baths of phosphate-buffered saline (PBS) for 5 min, the peroxidase color reaction was developed with diaminobenzidine-H 2 O 2 (DAB) and the nuclei were counter-stained with hematoxylin. Samples of ductal carcinoma in situ of the breast previously known to be positive for lectin histochemistry were used as positive controls, while the negative control was obtained by replacing the lectin with PBS and lectin inhibition with its specific sugar at a concentration of 300 mM [12,13]. All materials which source was not specified were obtained from SigmaAldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Reaction for CA IX was considered immunopositive when there was any indication of membrane staining, whereas HIF-1a expression was considered positive when there was nuclear staining in more than 10% of the cancer cells analyzed [16]. Stainings for Gal-1, Gal-3, SNA and L-PHA were considered positive when at least 10% of cells showed cellular reactivity, irrespective of cellular location [12,13,17]. For the evaluation of stromal cells, 10 fields under the 40 × objective lens were evaluated and any positive stromal cells were included in the counting.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior

Rêgo

Filho²,

Cordeiro³

et al. 2014

Folia Histochem Cytobiol.

Self Cite

View full text Add to dashboard Cite

Hypoxic areas in solid tumors are often associated with poor prognosis and resistance to chemotherapy. The aim of the study was to analyze the expression of galectin-1 (Gal-1), galectin-3 (Gal-3), sialic acid and b1-6 branched glycan structures in hypoxic environment of invasive ductal carcinoma (IDC) of the breast. We performed lectin histochemistry with phytohemagglutinin-L (L-PHA) and Sambucus nigra lectin (SNA); and immunohistochemistry for Gal-1, Gal-3, carbonic anhydrase IX, hypoxia-inducible factor, estrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor type-2 for 86 IDC samples. Patients with markers positive for hypoxia were mostly ER-negative (p = 0.003) and presented with more nodal invasion than the non-hypoxic group (p = 0.0439). Concerning the glycobiological aspects, the hypoxic group expressed more of Gal-3 (p = 0.0021) and SNA ligands (p = 0.0498), however, there was no association between lectin-and galectin-staining and clinical and histopathological data. Our results suggest a change in the glycomic profile of patients within hypoxic regions of IDC. However, further studies are needed to evaluate the role of lectin-and galectin-ligands in tumor's hypoxic environment, as well as their potential to be used as therapeutic targets. (Folia Histochemica et Cytobiologica 2014, Vol. 52, No. 2, 96-103) Key words: breast cancer; IDC; hypoxia; glycomic profile; galectins; lectin ligands; IHC; histochemistry Ĩ ntroduction Breast cancer is the most common cancer among women, accounting for 22% of new cases every year, and the second most common cancer world wide [1]. Moreover, as with most solid tumors, breast cancers often have central regions of hypoxia which are usually peri-necrotic [2]. Cells that survive in this adverse environment are typically resistant to radiotherapy and chemotherapy and differ from cells in areas with adequate blood supply [3,4]. Hypoxia-inducible factor 1a (HIF-1a) is the major modulator of hypoxic condition and is constitutively produced under low-oxygen conditions, which typically occurs at distances greater than 180 μm from blood vessel [5]. HIF-1a affects tumor progression and angiogenesis by modulating the expression of genes involved in the adaptation to oxygen-and nutrient-deficiency, leading to increased cell survival, inhibition of apoptosis and migration [6,7]. Among these genes, carbonic anhydrase IX (CA IX) and glucose transporter 1 (GLUT1) play crucial roles in cellular adaptation, by altering the energy metabolism of neoplastic cells, which begin to show high rates of anaerobic glycolysis [2,[5][6][7]. The change in metabolic profile is followed by altered expression of enzymes involved in aerobic and anaerobic glycolysis, sugar

show abstract

Implications on glycobiological aspects of tumor hypoxia in breast ductal carcinoma in situ

Cited by 14 publications

References 18 publications

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycomic profile of the human parotid gland between 18th and 26th week of fetal development

The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior

Contact Info

Product

Resources

About