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

Multiple myeloma (MM), a malignant plasma cell infiltration of the bone marrow, is generally considered incurable: resistance to multiple therapeutic drugs inevitably arises from tumor cell-intrinsic and tumor microenvironment (TME)-mediated mechanisms. Here we report that the proteoglycan tandem re...

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Detalles Bibliográficos
Autores principales: Huynh, Mailee, Chang, Hae Yeun, Lisiero, Dominique N., Ong, Irene M., Kashyap, Trinayan, Callander, Natalie S., Miyamoto, Shigeki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045543/
https://www.ncbi.nlm.nih.gov/pubmed/36480501
http://dx.doi.org/10.1371/journal.pone.0274704
Descripción
Sumario:Multiple myeloma (MM), a malignant plasma cell infiltration of the bone marrow, is generally considered incurable: resistance to multiple therapeutic drugs inevitably arises from tumor cell-intrinsic and tumor microenvironment (TME)-mediated mechanisms. Here we report that the proteoglycan tandem repeat 1 (PTR1) domain of the TME matrix protein, hyaluronan and proteoglycan link protein 1 (HAPLN1), induces a host of cell survival genes in MM cells and variable resistance to different classes of clinical drugs, including certain proteasome inhibitors, steroids, immunomodulatory drugs, and DNA damaging agents, in several MM cell lines tested. Collectively, our study identifies HAPLN1 as an extracellular matrix factor that can simultaneously confer MM cell resistance to multiple therapeutic drugs.