الفهرس | Only 14 pages are availabe for public view |
Abstract Breast cancer (BC) is the most common cancer and the leading cause of death in females worldwide. The tumor microenvironment (TME) is now recognized as an important factor in tumor development and progression, as well as a measurable parameter of treatment response. In TME, IL-6 that is essential for tumor cell proliferation and differentiation released by cancerous cells as well as other stromal cells. The elevated levels of this cytokine is typically associated with a poor prognosis and lower survival in breast cancer patients. The current study aimed at investigating the autophagic activities and level of cancer stem cells in breast cancer tumor microenvironment supplemented with anti-IL-6 monoclonal antibodies. This study was designed to investigate the immunotherapeutic effect of neutralizing the overexpressed IL-6 secreted within the breast cancer TME. The study was conducted on 20 patients with pathologically proved breast carcinoma who endue at modified radical mastectomy for histologically proved breast cancer from the department of experimental and clinical Surgery, Medical Research Institute, Alexandria University. Fresh sterile tissue from primary breast tumor as well as normal breast tissue from the same excised breast were obtained as surgical specimens from each patient immediately after surgical resection. Each tissue sample was cultured without and with appropriate concentration of anti-IL-6 mAb. Paraffin embedded cultured breast tumor and normal tissues were then evaluated for LC3B levels as a specific marker of autophagy. Levels of CD44 and CD24 expression were also measured as markers of CSCs in tumor and normal breast tissue samples using immunofluorescence technique. Results: The levels of autophagy as well as both CD44 and CD24 in our own designed breast tumor tissue culture system are significantly higher than that of the corresponding breast normal ones. These levels significantly decreased by neutralizing the IL-6 activities using anti-IL-6 mAbs. No significant correlations were found between CD44 and CD24 levels in all tissue culture systems except in the anti-IL-6 mAb treated tumor / normal one. While negative correlations between CD44 and CD24 levels in the anti-IL-6 mAb supplemented tissue culture systems may be due to shift in the dynamic equilibrium between CSCs and NSCCs No significant correlations were found between the autophagy level and either CD44 or CD24 levels in almost all tissue culture systems except the anti-IL-6 mAb tumor tissue culture ones. Accordingly, neutralization of IL-6 within breast cancer TME may represent a potential promising immunotherapeutic strategy of the disease through reduction of both autophagic activity and stemness of the tumor tissue. |