Effective impairment of myeloma cells and their progenitors by hyperthermia

نویسندگان

  • Hirokazu Miki
  • Shingen Nakamura
  • Asuka Oda
  • Hirofumi Tenshin
  • Jumpei Teramachi
  • Masahiro Hiasa
  • Ariunzaya Bat-Erdene
  • Yusaku Maeda
  • Masahiro Oura
  • Mamiko Takahashi
  • Masami Iwasa
  • Takeshi Harada
  • Shiro Fujii
  • Kiyoe Kurahashi
  • Sumiko Yoshida
  • Kumiko Kagawa
  • Itsuro Endo
  • Kenichi Aihara
  • Mariko Ikuo
  • Kohji Itoh
  • Koichiro Hayashi
  • Michihiro Nakamura
  • Masahiro Abe
چکیده

Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated "side population" fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

CD93 is Selectively Expressed on Human Myeloma Cells but Not on B Lymphocytes

Background: CD93 has originally been known as a C1q receptor, and many studies have demonstrated that CD93 is expressed on hematopoietic stem cells, B cell progenitors, myeloid and monocytic cells. Moreover, CD93 is shown to be expressed on long-lived plasma cells, and CD93 deficient-mice display an impairment in plasma cell development. Objective: To investiga...

متن کامل

Adult Hippocampal Neurogenesis and Memory

Adult neurogenesis, a concept emergent in the late 1990s, is the generation of new neurons in the adult brain. This process occurs thank to cells who have this proliferative feature, named as Neural Stem Cells (NSCs). Neural Stem Cells (NSCs) are primary progenitors who can generate the two neural types (neurons and glia). Classically it was assumed that NSCs are only present in the embryo, but...

متن کامل

Adult Hippocampal Neurogenesis and Memory

Adult neurogenesis, a concept emergent in the late 1990s, is the generation of new neurons in the adult brain. This process occurs thank to cells who have this proliferative feature, named as Neural Stem Cells (NSCs). Neural Stem Cells (NSCs) are primary progenitors who can generate the two neural types (neurons and glia). Classically it was assumed that NSCs are only present in the embryo, but...

متن کامل

Mandibular Swelling as the First Manifestation of Multiple Myeloma

Multiple myeloma is a monoclonal malignant proliferation of plasma cells. The disease is more frequent in men, and the average age of patients at the time of diagnosis of the disease is about 60 years. Solitary myeloma may be the first manifestation of the disseminated form of multiple myeloma, which is characterized by multiple skeletal lesions, general metabolic alterations, impairment of ren...

متن کامل

Fingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors

Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2018