Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams

Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams

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 challeng...

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Bibliographic Details
Main Authors: Francesco P. Cammarata, Giusi I. Forte, Giuseppe Broggi, Valentina Bravatà, Luigi Minafra, Pietro Pisciotta, Marco Calvaruso, Roberta Tringali, Barbara Tomasello, Filippo Torrisi, Giada Petringa, Giuseppe A. P. Cirrone, Giacomo Cuttone, Rosaria Acquaviva, Rosario Caltabiano, Giorgio Russo
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:International Journal of Molecular Sciences
Subjects:
triple-negative breast cancer (TNBC)
proton therapy
xenograft mice
microarray
Online Access:https://www.mdpi.com/1422-0067/21/17/6337
Description
Summary: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.
ISSN:1661-6596
1422-0067

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