TY - JOUR
T1 - Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams
AU - Cammarata, Francesco P.
AU - Forte, Giusi
AU - Broggi, Giuseppe
AU - Bravata, Valentina
AU - Minafra, Luigi
AU - Pisciotta, Pietro
AU - Calvaruso, Marco
AU - Tringali, Roberta
AU - Tomasello, Barbara
AU - Torrisi, Filippo
AU - Petringa, Giada
AU - Cirrone, Giuseppe A. P.
AU - Cuttone, Giacomo
AU - Acquaviva, Rosaria
AU - Caltabiano, Rosario
AU - Russo, Giorgio
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.
AB - Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.
KW - triple-negative breast cancer (TNBC)
KW - proton therapy
KW - xenograft mice
KW - microarray
KW - DOSE IONIZING-RADIATION
KW - THERAPY
KW - CELL
KW - MASTECTOMY
KW - RESISTANCE
KW - RISK
U2 - 10.3390/ijms21176337
DO - 10.3390/ijms21176337
M3 - Article
SN - 1422-0067
VL - 21
SP - 1
EP - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 6337
ER -