Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix

Area of Science:

• Oncology
• Biochemistry
• Cancer Biology

Background:

• Triple-negative breast cancer (TNBC) is aggressive and deadly, with radiation therapy as a standard treatment.
• The tumor microenvironment's response to radiation is poorly understood, despite its role in cancer progression.
• Collagen deposition is linked to poor prognosis in breast cancer, but isoform-specific changes post-radiation are unstudied.

Purpose of the Study:

• To investigate the impact of radiation on collagen isoform expression within the triple-negative breast cancer microenvironment.
• To determine if radiation influences the oncogenic potential of the tumor microenvironment.

Main Methods:

• Co-cultures of stromal fibroblasts, adipose-derived stem cells, and TNBC cells were established.
• Cultures were irradiated, followed by decellularization and reseeding with TNBC cells.
• Proteomic analysis using mass spectrometry was performed on the irradiated co-cultures.

Main Results:

• Irradiation of the TNBC co-culture led to a decrease in collagen VI levels.
• Collagen VI is an oncogenic collagen isoform associated with breast cancer progression.
• This suggests radiation may reduce the tumor microenvironment's oncogenic capacity.

Conclusions:

• Radiation therapy's anti-cancer effects extend beyond direct cell killing.
• Radiation can modulate the tumor microenvironment, potentially creating a less oncogenic milieu.
• Targeting collagen VI or its pathways could be a future therapeutic strategy in TNBC.