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Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts

Natalie C Direkze1, Kairbaan Hodivala-Dilke, Rosemary Jeffery

  • 1Cancer Research United Kingdom, London Research Institute, London, UK. natalie.direkze@cancer.org.uk

Cancer Research
|December 3, 2004
PubMed

Insights

Bone marrow contributes to myofibroblast populations in pancreatic tumors. This systemic response in tumor stroma suggests potential therapeutic targets for cancer therapy.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Tissue Repair

Background:

  • Myofibroblasts are crucial in tissue repair and fibrosis, but their origin remains debated.
  • Fibrocytes are circulating cells that may differentiate into myofibroblasts at injury sites.
  • Previous research identified bone marrow as a myofibroblast source in various organs, exacerbated by injury.

Purpose of the Study:

  • To investigate if bone marrow contributes to myofibroblast and fibroblast populations within pancreatic tumor stroma.
  • To explore the systemic contribution of bone marrow-derived cells to tumor microenvironment development.

Main Methods:

  • Utilized a RIPTag transgenic mouse model that spontaneously develops pancreatic beta-cell tumors (insulinoma).
  • Employed lineage tracing to identify donor-derived cells within the tumor stroma.
  • Quantified the contribution of bone marrow-derived myofibroblasts and fibroblasts to the tumor microenvironment.

Main Results:

  • Approximately 25% of myofibroblasts within pancreatic tumors were derived from the bone marrow donor.
  • Bone marrow-derived myofibroblasts were predominantly localized at the tumor periphery.
  • Demonstrated that tumor stroma development involves a systemic contribution from the bone marrow.

Conclusions:

  • The bone marrow is a significant source of myofibroblasts and fibroblasts contributing to pancreatic tumor stroma.
  • Tumor stroma formation is, in part, a systemic response involving bone marrow-derived cells.
  • These findings suggest potential therapeutic strategies targeting bone marrow-derived cells for pancreatic cancer treatment.

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