Regulation of multidrug resistance in cancer cells by hyaluronan

Suniti Misra1, Shibnath Ghatak, Alexandra Zoltan-Jones

  • 1Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Insights

Hyaluronan oligosaccharides suppress cancer cell survival pathways, enhancing chemotherapy effectiveness. This approach also shows intrinsic tumor growth suppression, offering a dual therapeutic strategy.

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Drug Resistance Mechanisms

Background:

  • Multidrug resistance (MDR) in cancer involves ATP-dependent efflux pumps and altered cell survival/apoptotic signaling.
  • Hyaluronan-tumor cell interactions influence cancer cell signaling and growth.
  • Previous work showed hyaluronan oligosaccharides suppress phosphoinositide 3-kinase/Akt pathway and reduce tumor growth.

Purpose of the Study:

  • To investigate the effect of hyaluronan oligosaccharides on multidrug resistant (MDR) tumor cells.
  • To determine if these oligosaccharides can sensitize MDR cells to chemotherapeutic drugs.
  • To explore the role of hyaluronan production and emmprin in inducing drug resistance.

Main Methods:

  • Treatment of MDR tumor cells with hyaluronan oligosaccharides.
  • Analysis of MAP kinase and phosphoinositide 3-kinase signaling pathways.
  • Assessment of sensitization to chemotherapeutic agents.
  • Investigation of increased hyaluronan production and emmprin expression effects on drug sensitivity.

Main Results:

  • Hyaluronan oligosaccharides suppressed both MAP kinase and phosphoinositide 3-kinase pathways in MDR tumor cells.
  • These oligomers sensitized MDR cells to various chemotherapeutic drugs.
  • Increased hyaluronan production and emmprin expression induced drug resistance in previously sensitive cells.

Conclusions:

  • Perturbation of hyaluronan signaling suppresses MDR tumor cell growth and sensitizes them to chemotherapy.
  • Hyaluronan signaling modulation offers a potential dual therapeutic strategy in cancer treatment.
  • Targeting hyaluronan pathways could overcome chemoresistance and inhibit tumor progression.

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