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Wnt and TLR4 Pathway modulators as a Promising Therapeutic Strategy in the Treatment of Glioblastoma
Author(s) -
Esposito Emanuela,
Casili Giovanna,
Campolo Michela,
Lanza Marika,
Filippone Alessia,
Cuzzocrea Salvatore
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.695.3
Subject(s) - wnt signaling pathway , claudin , cancer research , carcinogenesis , apoptosis , signal transduction , biology , glioma , u87 , microbiology and biotechnology , medicine , tight junction , cancer , genetics
Glioblastomas (GMB) are highly aggressive brain tumors. Despite recent improvements of care in the fields of surgical resection, radiotherapy and alkylating chemotherapy, the 5‐year survival rate for patients with GBM remains low and additional therapies are needed. Various pathways are involved in glioma tumorigenesis, among which the Wingless (Wnt) signaling. Dickkopf protein‐related protein 3 (Dkk‐3) interacts with proteins of Wnt pathway as inhibitor. The Wnt signaling contributes to activity of the claudins, important components of Tight junctions (TJ), implicated in blood‐brain barrier (BBB) formation, whose expression was altered selectively in cerebral microvessels of human GBM. The aim of this study was to determine the role of Wnt pathways to directly regulate tumor grown, apoptosis process by targeting Dkk‐3, TJ alteration involving claudin‐5 and to suggest possible therapeutic interactions involving Wnt/Toll‐like receptors (TLRs) pathways. In the present study we investigated the expression of Dkk‐3, Claudin‐5, apoptosis markers and TLR‐4 receptor protein levels in in vitro studies on U‐138MG and A‐172 human glioma cell lines and in GBM human patient's tissues. We showed a significant Dkk‐3 and claudin‐5 down regulation, with the apoptosis process involvement and with an interesting TLR‐4/Wnt modulation. We concluded that Wnt and TLR4 pathway modulators might shift the balance from tumor growth stasis to cytotoxic responses, representing a promising approach in the treatment of glioblastoma. Support or Funding Information No founding This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .