Mitochondrial Horizontal Transfer in Triple Negative Breast Cancer

Abstract

Cancer cells constantly interact with surrounding cells in the tumor. The communication between cancer cells and surrounding cells is often the reason behind the failure of cancer therapeutics. We seek to understand this communication in an effort to overcome these barriers. Macrophages are a component of the immune system. Their best known function is to seek and destroy foreign particles. However, in the tumor environment, macrophages have a very different role macrophages can facilitate steps of metastasis by communicating with cancer cells and helping cancer cells leave the tumor, enter the blood stream, and grow at the metastatic site. We discovered that macrophages transfer mitochondria to triple negative breast cancer cells, regulating cancer cell proliferation. We polarized macrophages to an M2-like state and found increased mitochondrial transfer to cancer cells. Furthermore, increasing and decreasing mitochondrial fragmentation in macrophages by overexpressing and inhibiting a key mitochondrial fission machinery player, DRP-1, led to increased and decreased mitochondrial transfer, respectively. We are now optimizing conditions to assess macrophage mitochondrial transfer to patient-derived cells, and are performing experiment to mechanistically understand how macrophage mitochondrial transfer leads to increased breast cancer cell proliferation.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2021
Accession Number
AD1154922

Entities

People

  • Chelsea Kidwell
  • Daniel Greiner
  • Joseph Casalini
  • Julio Fierro
  • Minna Roh-johnson

Organizations

  • University of Utah

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Biochemistry
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Data Analysis
  • Fragmentation
  • Macrophages
  • Medical Personnel
  • Metastasis
  • Mitochondria
  • Myeloid Cells
  • Neoplasms
  • Organoids
  • Standards
  • Students
  • Xenografts

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Immunology
  • Molecular Biology and Genetics