Expression of CD44s, CD44v6, and Hyaluronan Across the Spectrum of Normal-hyperplasia-carcinoma in Breast

Afify, Alaa M; McNiel, Maaya A.; Braggin, Jacquelyn; Bailey, Helen; Paulino, Augusto F. G.

doi:10.1097/pai.0b013e318047df6d

Cited by 28 publications

(30 citation statements)

References 42 publications

(38 reference statements)

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“…All isoforms of the protein are encoded by a single gene but are derived by alternative splicing (v1-v10) and variation in Oand N-glycosylations (47,48). CD44s, the smallest and most widely expressed isoform, is expressed in ductal epithelial cells and myoepithelial cells in all cases of normal and benign breast tissue; however, the expression of CD44s progres-sively decreases with increasing deviation from normal histology corresponding to our data (49). The peptides identified by our study were identical to protein sequences in both the N-terminal part (exon 2) and the C-terminal part of CD44, sequences present in all CD44 isoforms.…”

Section: Discussioncontrasting

confidence: 52%

Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry

Leth-Larsen

Lund

Hansen

et al. 2009

Molecular & Cellular Proteomics

110

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The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multistep process. The cancer cell proteins and plasma membrane proteins in particular involved in this process are poorly defined, and a study of the very early events of the metastatic process using clinical samples or in vitro assays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice; but although one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane purification and comparative quantitative LC-MS/MS proteomics identified 13 membrane proteins that were expressed at higher levels and three that were underexpressed in the metastatic compared with the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5-nucleotidase (CD73), NDRG1, integrin ␤1, CD44, CD74, and major histocompatibility complex class II proteins. The altered expression levels of proteins identified by LC-MS/MS were validated using flow cytometry, Western blotting, and immunocyto-and immunohistochemistry. Analysis of clinical breast cancer biopsies demonstrated a significant correlation between high ecto-5-nucleotidase and integrin ␤1 expression and poor outcome, measured as tumor spread or distant recurrence within a 10-year follow-up. Further the tissue analysis suggested that NDRG1, HLA-DR␣, HLA-DR␤, and CD74 were associated with the ER

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Section: Discussioncontrasting

confidence: 52%

Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry

Leth-Larsen

Lund

Hansen

et al. 2009

Molecular & Cellular Proteomics

110

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“…Although overexpression of CD44v6 has been reported in intestinal metaplasia of gastric mucosa, 45 to the best of our knowledge, this is the first time that overexpression of CD44v6 is described in hyperplastic lesions of the stomach. In other epithelial tissues such as the lung, 46 endometrium 47,48 and breast, 49 expression of CD44v6 in hyperplasia has already been observed. It remains to be clarified whether the overexpression of CD44v6 in hyperplastic/hyperproliferative lesions of gastric mucosa may indicate early premalignant changes not only in the abovementioned organs but also in the stomach.…”

Section: Cd44v6 In Gastric Cancermentioning

confidence: 99%

De novo expression of CD44 variants in sporadic and hereditary gastric cancer

Cunha

Oliveira

Wen

et al. 2010

Laboratory Investigation

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CD44 is the major ubiquitously expressed cell surface receptor for hyaluronate. The CD44 gene encodes several protein isoforms due to extensive alternative splicing and post-translational modifications. Some of these CD44 variable isoforms have been foreseen as key players in malignant transformation and their expression is highly restricted and highly specific, unlike the canonical CD44 standard isoform. In this study, we aimed at dissecting the mRNA splicing pattern of CD44 in normal stomach and gastric cancer (GC) cell lines (n ¼ 9) using cloning and quantitative mRNA amplification assays. Moreover, we assessed the RNA levels and protein expression pattern of relevant splicing forms in distinct premalignant and malignant gastric lesions (sporadic (n ¼ 43) and hereditary (n ¼ 3) forms) using real-time RT-PCR and immunohistochemistry. We also explored the association of CD44 and E-cadherin expression by immunohistochemistry, as E-cadherin has a pivotal functional role in GC. We established the pattern of CD44 variant forms in normal stomach and gastric malignancy. We observed that although exon v6-containing isoforms were rarely expressed in normal gastric mucosa, they became increasingly expressed both in gastric premalignant (hyperplastic polyps, complete and incomplete intestinal metaplasia, low-and high-grade dysplasia) and malignant lesions (cell lines derived from GCs, primary sporadic GCs and hereditary diffuse GCs (HDGCs)). Moreover, we verified that whenever E-cadherin expression was absent, exon v6-containing CD44 isoforms were overexpressed. The lack of expression of CD44 isoforms containing exon v6 in the surface and foveolar epithelia of normal stomach and, its de novo expression in premalignant, as well as in sporadic and hereditary malignant lesions of the stomach, pinpoint CD44 v6-containg isoforms as potential biomarkers for early transformation of the gastric mucosa. Further, our results raise the hypothesis of using CD44v6 as a marker of early invasive intramucosal carcinoma in HDGC CDH1 mutation carriers that lack CDH1 expression in their tumors.

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“…Also, HA was exclusively confined to the stroma in all cases of breast cancer and was not detected in epithelial cells. [16] However, in our study, HA was expressed in a tumor and stroma. Consistent with our finding, the expression of HA is correlated with malignancy in many cancers such as breast, lung and ovarian cancer.…”

Section: Discussionmentioning

confidence: 41%

“…Contradictory to our finding, Afify et al found HA tends to be expressed at the periphery of invasive tumor islands than the center, these findings supporting the argument that tumors release many soluble factors that increase HA. [16,66] In the present study, hyaluronan intensity of expression in tumor islands and stroma revealed significant differences among the studied different histological grades and types (p < .05). A Higher number of the examined SCC variant cases revealed strong HA expression in comparison with conventional SCC type.…”

Section: Discussionmentioning

confidence: 81%

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N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

Hendawy

Ibrahiem

et al. 2017

JST

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Background: Epithelial-mesenchymal transition (EMT) is regarded as an essential step for tumor invasion and metastasis. In squamous cell carcinoma of head and neck (HNSCC), N-Cadherin expression and its involvement in tumor progression remains a controversial topic. Aim of the study: The present study aimed to assess the expression of N-cadherin and HA in HNSCC and further study their relation to patients survival and outcomes. Material and methods: Fifty-eight retrospective selected cases of head and neck squamous carcinomas (HNSCCs) with available paraffin blocks. Complete clinico-pathological and follow-up data were recorded. Immune staining for N-cadherin and hyaluronan were done, also, we study the correlation of the results with patients survival data. Results: Squamous cell carcinoma islands demonstrated high N-cadherin expression in 55.2% and low expression in 44.8%. N-cadherin high expression was significantly (p < .05) associated with large tumor sizes, advanced TNM clinical stage, increased incidence of recurrence and patient's death. A significant correlation was recorded between the presence of neural invasion and N-cadherin expression (p = .004). Strong intensity of stromal HA was significantly (p < .05) associated with an oral site, nodal metastasis, and higher TNM stage. Patients with high N-cadherin expression, diffuse hyaluronan, and strong stromal hyaluronan reaction had significantly lower DFS rates (p < .05). High N-cadherin expression, diffuse hyaluronan immunoreactivity, and strong stromal hyaluronan reaction intensity had significantly lower OS rates (p < .05). Conclusion: N-cadherin and hyaluronan could be important and promising biomarkers during surveillance of patients with HNSCC.

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Expression of CD44s, CD44v6, and Hyaluronan Across the Spectrum of Normal-hyperplasia-carcinoma in Breast

Abstract: This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.

Cited by 28 publications

References 42 publications

Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry

Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry

De novo expression of CD44 variants in sporadic and hereditary gastric cancer

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

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