Activation of Inflammatory Responses Correlate With Hedgehog Activation and Precede Expansion of Cancer Stem-Like Cells in an Animal Model of Residual Triple Negative Breast Cancer after Neoadjuvant Chemotherapy. Previously,. In addition, chemotherapy can induce an inflammatory response and inflammatory factors can lead to activation of Hedgehog at sites of tissue injury.
Following treatment, tumor volume decreased reaching a nadir around 15 days after the start of treatment and increased back to pre-treatment size 35- 9 days post treatment. Immunohistochemical staining of mice tumors revealed that Sonic hedgehog and nuclear Gli-1 expression transiently increased following docetaxel treatment.
Thus, chemotherapy treatment resulted in activation of the hedgehog pathway and release of inflammatory cytokines leading to long-term expansion of ALDH1A3 positive stem cells, which can contribute to the regrowth of the tumor and promote resistance to treatment.
In particular, abnormal regulation of the Hedgehog pathway can alter cellular proliferation and differentiation leading to tumorigenesis. Eight week-old female Nonobese diabetic/severe combined immunodeficiency Patient Derived Xenografts tumor bearing mice with a P1-P3 fragment of a human patient derived breast cancer xenograft TM00089 implanted subcutaneously. Slides were deparaffinized in Citrasolv and rehydrated in ethanol at decreasing concentrations and 80% for ending in distilled water for 30 s.
Cancer Stud Mol Med Open J. 2015; 2(2): 80-86. doi: 10.17140/CSMMOJ-2-112
