High expression of Lewisy/bantigens is associated with decreased survival in lymph node negative breast carcinomas

Madjd, Zahra; Parsons, Tina; Watson, Nicholas; Spendlove, Ian; Ellis, Ian O.; Durrant, Lindy G.

doi:10.1186/bcr1305

Cited by 85 publications

(69 citation statements)

References 21 publications

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“…LeY antigen is considered a primary target of cancer therapy using humanized monoclonal antibodies (33)(34)(35) and by cancer vaccine with LeY mimicry peptide (36, 37). Our study supports strategies targeting LeY antigen in breast, lung, ovary, and colon cancers (6,38,39).…”

Section: Discussionmentioning

confidence: 59%

Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells

Hatakeyama

Sato

Nakayama

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Cell surfaces of epithelial cancer are covered by complex carbohydrates, whose structures function in malignancy and metastasis. However, the mechanism underlying carbohydrate-dependent cancer metastasis has not been defined. Previously, we identified a carbohydrate-mimicry peptide designated I-peptide, which inhibits carbohydrate-dependent lung colonization of sialyl Lewis X-expressing B16-FTIII-M cells in E/P-selectin doubly-deficient mice. We hypothesized that lung endothelial cells express an unknown carbohydrate receptor, designated as I-peptide receptor (IPR), responsible for lung colonization of B16-FTIII-M cells. Here, we visualized IPR by in vivo biotinylation, which revealed that the major IPR is a group of 35-kDa proteins. IPR proteins isolated by I-peptide affinity chromatography were identified by proteomics as Ser/Arg-rich alternative pre-mRNA splicing factors or Sfrs1, Sfrs2, Sfrs5, and Sfrs7 gene products. annexin ͉ galectin ͉ metastasis ͉ selectin ͉ vasculature T he apical cell surface of epithelia is covered by numerous carbohydrates attached to membrane proteins and lipids. When epithelial cells are transformed, the structure of these carbohydrates changes (1). Many investigators have suggested a correlation between cancer-associated carbohydrate antigens and poor patient prognosis, including metastasis (2-8). Despite extensive structural analysis and clinical observations using monoclonal antibodies against cancer-associated carbohydrate antigens, mechanisms underlying carbohydrate-dependent cancer metastasis through the circulation remain elusive. Because E-selectin is expressed on the inflammatory endothelial cell surface and binds to cancer-associated carbohydrate antigens such as sialyl Lewis A (sLeA) and sialyl Lewis X (sLeX), E-selectin provides a mechanism for sLeA and/or sLeX antigenexpressing cancer cells to be metastasized through the hematogenous route (4-6). Involvement of P-selectin and L-selectin in cancer metastasis has been also described (7,8). However, substantial clinical data indicate the existence of selectin-independent but carbohydrate-dependent cancer metastasis (6, 10, 11).In our previous studies, we screened a peptide-displaying phage library using a monoclonal anti-Lewis A antibody (clone 7LE) and identified a short peptide IELLQAR, designated I-peptide (12-14). When I-peptide was injected intravenously into a mouse, it bound to a specific subset of lung capillary endothelial cells but not to blood vessels of other organs including the liver (12). I-peptide administration inhibited carbohydrate-dependent lung colonization of fucosyltransferase-3-transfected sialyl Lewis X antigenpositive B16 (B16-FTIII-M) cells (15) in wild-type mice (12) and in E-and P-selectin doubly-deficient mutant mice (13), suggesting that the lung endothelial surface expresses unknown carbohydratebinding receptor(s) enabling colonization of B16-FTIII-M cells. We designated this presumptive receptor I-peptide receptor (IPR) (13).In this study, we isolated IPR candidate proteins by I-peptideaff...

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Section: Discussionmentioning

confidence: 59%

Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells

Hatakeyama

Sato

Nakayama

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…After surgical treatment, patients with an NPI score B3.4 received no adjuvant therapy, those with a NPI score [3.4 received Tamoxifen if oestrogen receptor (ER) positive (± Zoladex if pre-menopausal) or classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) if ER negative and fit enough to tolerate chemotherapy [27]. Patients that received breast conserving surgery or mastectomy may receive a course of radiotherapy according to the risk of regional recurrence that is determined by the multidisciplinary team.…”

Section: Patients and Specimensmentioning

confidence: 99%

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Mohammed

Ellis

Elsheikh

et al. 2008

Breast Cancer Res Treat

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Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors, relationship with angiogenesis and whether active lymphangiogenesis occurs within the tumour. A series of 177 well-characterized breast cancers, with long term follow up, were stained with D2-40, CD31 and CD34. Distribution of lymphatics and lymph vessel density (LVD) were assessed in three areas, intratumoural, peripheral and peritumoural and correlated with clinicopathological criteria and patient prognosis. Microvessel density (MVD) was assessed and correlated with LVD. Double immunohistochemical staining with D2-40 and MIB-1 was carried out to assess the proliferative status of lymphatics and of the tumour emboli within. Peritumoural lymphatics were detected in all tumours whereas peripheral and intratumoural lymphatics were detected in 86 and 41% of specimens, respectively. Tumours with higher total LVD were significantly associated with the presence of lymph node (LN) metastasis and shorter overall survival (OS). In multivariate analysis, tumour grade, LN status and the presence of lymphovascular invasion, but not LVD, were independent poor prognostic factors. No association was found between LVD and MVD. Proliferating lymphatics were detected in 29% of specimens and were significantly associated with dense inflammatory infiltrate. In conclusion, lymphatics are located primarily in the peritumoural and peripheral areas in breast cancer and seem to play an important role in disease progression by being routes for tumour dissemination. The lack of correlation between lymphangiogenic and angiogenic characteristics suggests two distinct processes and the presence of active lymphangiogenesis, albeit in a small portion of specimens, may have important therapeutic implications.Keywords Angiogenesis Á Breast cancer Á D2-40 Á Lymphangiogenesis and prognosis Introduction and aims

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“…Patient management was based on tumour characteristics provided by the Nottingham Prognostic Index (NPI) and hormone receptor status. Patients with an NPI score p3.4 received no adjuvant therapy, those with a NPI score 43.4 received tamoxifen if oestrogen receptor (ER) positive: (±Zoladex if pre-menopausal) or classical cyclophosphamide, methotrexate and 5-fluorouracil if ER negative and fit enough to tolerate chemotherapy (Madjd et al, 2005). Tumours were graded according to a modified Bloom -Richardson scoring system (Elston and Ellis, 1991) and size was categorised according to the TNM staging criteria (Singletary and Connolly, 2006).…”

Section: Patient Datamentioning

confidence: 99%

Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype

et al. 2008

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Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast cancer-specific survival; however, this was not independent from other traditional markers on multivariate analysis. Our results demonstrate that both CAV1 and CAV2 are associated with basal-like phenotype. Further studies are warranted to determine whether they play an oncogenic role in basal-like/triple-negative breast cancer development or are just surrogate markers for this subgroup.

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High expression of Lewisy/bantigens is associated with decreased survival in lymph node negative breast carcinomas

Cited by 85 publications

References 21 publications

Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells

Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

Caveolin 1 and Caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype

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