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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
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Tumor-associated fibroblasts promote the proliferation and decrease the doxorubicin sensitivity of liposarcoma cells.

Kamran Harati1, Adrien Daigeler1, Tobias Hirsch1

  • 1Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, D-44789 Bochum, Germany.

International Journal of Molecular Medicine
|April 16, 2016
PubMed
Summary

Tumor-associated fibroblasts (TAFs) from liposarcomas significantly increase cancer cell proliferation and reduce chemoresistance to doxorubicin. TAFs from high-grade tumors had a greater effect, highlighting the tumor microenvironment

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Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Liposarcomas exhibit distinct chemoresistance and high local recurrence rates.
  • Current first-line chemotherapy with doxorubicin shows limited efficacy (approx. 36% response rate).
  • Local recurrences occur frequently even after complete surgical resection.

Purpose of the Study:

  • To investigate the impact of tumor-associated fibroblasts (TAFs) from liposarcomas on liposarcoma cell behavior.
  • To assess how TAFs influence liposarcoma cell proliferation, viability, and chemoresistance.
  • To compare the effects of TAFs from intermediate-grade versus high-grade liposarcomas.

Main Methods:

  • Isolation of intratumoral TAFs from intermediate- and high-grade liposarcoma samples.
  • Co-culture of human liposarcoma SW872 cells with isolated TAFs or dermal fibroblasts (control).
  • Assessment of SW872 cell proliferation (BrdU assay), viability (MTT assay), and doxorubicin sensitivity (iCELLigence system).

Main Results:

  • Co-culture with TAFs significantly increased SW872 cell proliferation and viability compared to control fibroblasts.
  • SW872 cells co-cultured with TAFs showed diminished sensitivity to doxorubicin.
  • TAFs from high-grade liposarcomas induced greater proliferation and chemoresistance than those from intermediate-grade liposarcomas.

Conclusions:

  • Tumor-associated fibroblasts significantly enhance liposarcoma cell proliferation and reduce chemosensitivity.
  • The grade of liposarcoma correlates with the TAFs' ability to promote tumor progression.
  • These findings underscore the critical role of the tumor microenvironment in liposarcoma and suggest TAFs as potential therapeutic targets.