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Systemic Mobilization of Breast Cancer Resistance Protein in Response to Oncogenic Stress

Małgorzata Szczygieł1, Marcin Markiewicz1, Milena Julia Szafraniec1,2

  • 1Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.

Cancers
|January 21, 2022
PubMed

Insights

A growing tumor upregulates breast cancer resistance protein (BCRP) in normal organs, enhancing drug efflux. This systemic response, possibly cytokine-mediated, may explain early multidrug resistance (MDR) in cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Breast cancer resistance protein (BCRP, or ABCG2) is crucial in cancer multidrug resistance (MDR).
  • BCRP facilitates the transport of hydrophobic compounds, including anti-cancer drugs.
  • Tumor growth can influence host physiology and drug response.

Purpose of the Study:

  • To investigate the systemic effects of tumor growth on BCRP expression in host organs.
  • To understand the relationship between tumor burden, BCRP levels, and cytokine profiles.
  • To elucidate the role of systemic BCRP upregulation in the development of primary MDR.

Main Methods:

  • Utilized a mouse model with subcutaneously growing tumors.
  • Analyzed BCRP expression at both transcriptional and translational levels in normal host organs.
  • Measured BCRP substrate efflux and peripheral blood cytokine levels.

Main Results:

  • Subcutaneous tumor growth significantly altered BCRP expression in distant normal organs.
  • BCRP transcript and protein levels correlated with tumor size and peripheral cytokine concentrations.
  • Enhanced efflux of BCRP substrates was observed in host tissues.
  • Systemic BCRP upregulation occurred early in tumor development.

Conclusions:

  • Oncogenic stress induces transient, systemic BCRP upregulation in host tissues, potentially mediated by cytokines.
  • This mechanism may contribute to the induction of primary multidrug resistance.
  • BCRP mobilization represents a potential universal defense strategy against various stresses.
  • Findings offer insights into cancer-host interactions, impacting cancer therapy and drug design.
Keywords:
ABGD2 upregulationcancer multidrug resistancecytokinesdrug effluxxenobiotic transport

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