Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Orfanelli Theofano
Dissertation committee:
Χρήστος Μπακογιάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Ζωγράφος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Θεοδωρόπουλος, Αναπληρωτής Καθηγητής , Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Ζαγουρή, Αναπληρώτρια Καθηγήτρια , Ιατρική Σχολή ,ΕΚΠΑ
Νικόλαος Μιχαλόπουλος, Επίκουρος Καθηγητής , Ιατρική Σχολή, ΕΚΠΑ
Μιχάλης Κοντός, Αναπληρωτής Καθηγητής , Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Κόντζογλου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Προγνωστική αξία και ρόλος ανοσολογικών και αγγειογενετικών παραγόντων του κυτταρικού μηχανισμού της αυτοφαγίας στον καρκίνο του μαστού.
Translated title:
Prognostic value and role of immunological and angiogenetic factors in the cellular mechanism of autophagy in breast cancer.
Summary:
The peripheral blood mononuclear cells (PBMCs) (monocytes, macrophages, lymphocytes) are activated when the immune system is
exposed to adverse physiological conditions (e.g.infection, inflammation,
trauma, stress, deprivation of nutrients ,cancer) to support the defense of the body and maintain cellular homeostasis. The 70kDa heat stock protein (Hsp70) is produced to maintain the function of proteins and activates an immune response. Autophagy is a cellular mechanism that
the cell uses to metabolize and recycle proteins and organelles to provide sufficient nutrients in response to accelerated gene activation.
Recent studies have shown that autophagy plays an important role in
development and progression of breast cancer as well as in response to chemotherapy. Considering the above , we designed a series of experiments to investigate the interplay between the mechanism of the
autophagy with cytokines and angiogenetic factors in breast cancer.
we tested the hypothesis that PBMCS respond to the presence of a malignant breast mass by increasing production of inflammatory and
pro-inflammatory markers. Specifically , we used the enzyme -linked
immunosorbent assay (ELISA) to assay the expression of IFN-γ, TNF-α ,
IL-β, IL-4, IL-10, LPA, Hsp70, in PBMCs from women who were diagnosed
with breast cancer or benign breast mass. We found statistically significant differences in the levels of the expression of Hsp70 and p62.
Specifically , women with breast cancer had higher levels of extracellular
Hsp70 in the serum. Additionally, the mean intracellular Hsp70 levels were higher in PBMCs from women with a malignant lesion than in women with a benign mass. Finally , in women with breast cancer the mean p62 level was 0.6 ng/ml, while in women with a benign breast mass the mean p62 level was significantly lower , 2.3 ng/ml.
According to the literature p62 is inversely related to the level of autophagy . This indicates that autophagy is higher in PBMCs from women with a malignant breast lesion , contributing to the survival of breast cancer cells.
Moreover, we found that the level of expression of autophagy in MBMCs from women with breast cancer is proportional to the intracellular levels
of Hsp70 in the same cells. We can speculate that the trigger that caused
an increase in the levels of expression of Hsp70 in women with breast cancer can also activate the mechanism of autophagy in PBMCs thus
affecting the tumorigenesis and response to chemotherapy and immunotherapy.
Finally, the detection of high levels of expression of Hsp70 and autophagy in PBMCs, as well as , the higher levels of Hsp70 in the
serum, can potentially be used as biomarkers in a non -invasive approach to triage preoperatively women with breast cancer
from women with benign breast mass.
Main subject category:
Health Sciences
Keywords:
Immune system, Autophagy, Breast cancer, Cytokines, Angiogenetic factors
Number of references:
143
