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HAPLN1 confers multiple myeloma cell resistance to several classes of therapeutic drugs

Mailee Huynh1,2, Hae Yeun Chang1,2, Dominique N Lisiero1,2

  • 1Department of Oncology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States of America.

Plos One
|December 8, 2022
PubMed

Insights

Hyaluronan and proteoglycan link protein 1 (HAPLN1) in the tumor microenvironment (TME) promotes multiple myeloma cell survival. This extracellular matrix protein confers resistance to various cancer drugs, presenting a challenge in myeloma treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Multiple myeloma (MM) is a bone marrow cancer characterized by plasma cell proliferation.
  • Therapeutic resistance is a major challenge in MM, often involving tumor cell-intrinsic and tumor microenvironment (TME) factors.
  • The TME plays a critical role in MM progression and drug resistance.

Purpose of the Study:

  • To investigate the role of hyaluronan and proteoglycan link protein 1 (HAPLN1) in mediating drug resistance in multiple myeloma.
  • To identify specific domains of HAPLN1 involved in inducing cell survival and resistance mechanisms.

Main Methods:

  • Utilized multiple myeloma cell lines.
  • Investigated the effect of the proteoglycan tandem repeat 1 (PTR1) domain of HAPLN1.
  • Assessed induction of cell survival genes.
  • Evaluated resistance to various classes of clinical drugs, including proteasome inhibitors, steroids, immunomodulatory drugs, and DNA damaging agents.

Main Results:

  • The PTR1 domain of HAPLN1 was found to induce cell survival genes in MM cells.
  • HAPLN1 conferred variable resistance to multiple classes of therapeutic drugs in tested MM cell lines.
  • This resistance was observed against proteasome inhibitors, steroids, immunomodulatory drugs, and DNA damaging agents.

Conclusions:

  • HAPLN1 is identified as an extracellular matrix factor contributing to multiple myeloma drug resistance.
  • The PTR1 domain of HAPLN1 plays a key role in conferring simultaneous resistance to diverse therapeutic agents.
  • Targeting HAPLN1 or its interactions may offer novel therapeutic strategies for overcoming drug resistance in multiple myeloma.

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