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Lectin RCA-I specifically binds to metastasis-associated cell surface glycans in triple-negative breast cancer
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  • 作者:Shu-Min Zhou (1) (2) (4)
    Li Cheng (1) (2) (3)
    Shu-Juan Guo (1) (2)
    Yang Wang (4)
    Daniel M Czajkowsky (3)
    Huafang Gao (5)
    Xiao-Fang Hu (3)
    Sheng-Ce Tao (1) (2) (3)

    1. Shanghai Center for Systems Biomedicine
    ; Key Laboratory of Systems Biomedicine (Ministry of Education) ; Shanghai Jiao Tong University ; 800 Dongchuan Road ; Shanghai ; 200240 ; China
    2. State Key Laboratory of Oncogenes and Related Genes
    ; Shanghai Jiao Tong University ; 800 Dongchuan Road ; Shanghai ; 200240 ; China
    4. Institute for Microsurgery of Limbs
    ; Shanghai Sixth hospital ; Shanghai Jiao Tong University ; 800 Dongchuan Road ; Shanghai ; 200240 ; China
    3. Bio-ID Center
    ; School of Biomedical Engineering ; Shanghai Jiao Tong University ; 800 Dongchuan Road ; Shanghai ; 200240 ; China
    5. Human Genetic Resource Center
    ; National Research Institute for Family Planning ; 12 Dahuisi Road ; Beijing ; 100081 ; China
  • 刊名:Breast Cancer Research
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:17
  • 期:1
  • 全文大小:2,176 KB
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  • 刊物主题:Cancer Research; Oncology;
  • 出版者:BioMed Central
  • ISSN:1465-5411
文摘
Introduction Triple-negative breast cancer (TNBC) patients often face a high risk of early relapse characterized by extensive metastasis. Previous works have shown that aberrant cell surface glycosylation is associated with cancer metastasis, suggesting that altered glycosylations might serve as diagnostic signatures of metastatic potential. To address this question, we took TNBC as an example and analyzed six TNBC cell lines, derived from a common progenitor, that differ in metastatic potential. Methods We used a microarray with 91 lectins to screen for altered lectin bindings to the six TNBC cell lines. Candidate lectins were then verified by lectin-based flow cytometry and immunofluorescent staining assays using both TNBC/non-TNBC cancer cells. Patient-derived tissue microarrays were then employed to analyze whether the staining of Ricinus communis agglutinin I (RCA-I), correlated with TNBC severity. We also carried out real-time cell motility assays in the presence of RCA-I. Finally, liquid chromatography-mass spectrometry/tandem spectrometry (LC-MS/MS) was employed to identify the membrane glycoproteins recognized by RCA-I. Results Using the lectin microarray, we found that the bindings of RCA-I to TNBC cells are proportional to their metastatic capacity. Tissue microarray experiments showed that the intensity of RCA-I staining is positively correlated with the TNM grades. The real-time cell motility assays clearly demonstrated RCA-I inhibition of adhesion, migration, and invasion of TNBC cells of high metastatic capacity. Additionally, a membrane glycoprotein, POTE ankyrin domain family member F (POTEF), with different galactosylation extents in high/low metastatic TNBC cells was identified by LC-MS/MS as a binder of RCA-I. Conclusions We discovered RCA-I, which bound to TNBC cells to a degree that is proportional to their metastatic capacities, and found that this binding inhibits the cell invasion, migration, and adhesion, and identified a membrane protein, POTEF, which may play a key role in mediating these effects. These results thus indicate that RCA-I-specific cell surface glycoproteins may play a critical role in TNBC metastasis and that the extent of RCA-I cell binding could be used in diagnosis to predict the likelihood of developing metastases in TNBC patients.

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