Impact of Proton Irradiation Depending on Breast Cancer Subtype in Patient-Derived Cell Lines

Int J Mol Sci. 2024 Sep 29;25(19):10494. doi: 10.3390/ijms251910494.

Abstract

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

Keywords: breast cancer; oncology; proton therapy; radiobiology; tumor microenvironment.

MeSH terms

  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / radiotherapy
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Cancer-Associated Fibroblasts / radiation effects
  • Cell Line, Tumor
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Histones / metabolism
  • Humans
  • MCF-7 Cells
  • Proton Therapy
  • Protons
  • Radiation Tolerance
  • Radiation, Ionizing
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / radiotherapy
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Protons
  • Histones
  • Tumor Suppressor Protein p53