Transgelin is upregulated in stromal cells of lymph node positive breast cancer
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26639304
DOI
10.1016/j.jprot.2015.11.025
PII: S1874-3919(15)30198-6
Knihovny.cz E-zdroje
- Klíčová slova
- Breast cancer, Lymph node metastasis, Proteomics, Transgelin, Transgelin-2,
- MeSH
- buňky stromatu metabolismus patologie MeSH
- lidé MeSH
- lymfatické uzliny metabolismus patologie MeSH
- mikrofilamentové proteiny metabolismus MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové proteiny metabolismus MeSH
- nádory prsu metabolismus patologie MeSH
- pilotní projekty MeSH
- regulace genové exprese u nádorů MeSH
- stupeň nádoru MeSH
- svalové proteiny metabolismus MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mikrofilamentové proteiny MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
- svalové proteiny MeSH
- transgelin MeSH Prohlížeč
UNLABELLED: Transgelin and transgelin-2 have been discussed as potential markers of various cancers. Here we identified increased transgelin level in lymph node positive vs. negative, low grade primary breast cancer tissues using 2-DE in the cohort of 12 patients. We further clinically validated 2-DE results in an independent cohort of 48 low grade breast cancer patients through untargeted and targeted proteomics analysis (iTRAQ-2D-LC-MS/MS, mTRAQ-SRM), at transcript level and using immunohistochemistry. Another group of 48 high grade tumors of different breast cancer subtypes was analyzed together with the low grade samples to test transgelin specificity for low grade tumors and to study transgelin relation to known molecular markers and histological features. The results confirmed transgelin connection with the lymph node metastasis. As a marker of a reactive tumor stroma, transgelin can be connected with the higher risk of metastasis development. Moreover, we observed significant down-regulation of transgelin in high vs. low grade tumors caused by decreased content of stromal cells (mainly expressing transgelin) in high grade tumor tissue. We also analyzed expression of transgelin-2 in the second cohort using proteomics and immunohistochemistry. Transgelin-2 was mainly expressed by epithelial cancer cells and its levels were increased in metastatic and poorly differentiated tumors. BIOLOGICAL SIGNIFICANCE: Both transgelin and transgelin-2 have been previously described as potential markers of many types of cancer. We are specifying this connection to metastatic affection of lymph nodes and cell differentiation in breast cancer. In the wider context, the results of our study highlight tumor stroma as a source of cancer biomarkers and point out how measured levels of tissue markers can actually reflect cellular feature of cancer mass.
Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic
Masaryk Memorial Cancer Institute Regional Centre for Applied Molecular Oncology Brno Czech Republic
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