Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP)

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP). / Fairfield, Heather; Dudakovic, Amel; Khatib, Casper M; Farrell, Mariah; Costa, Samantha; Falank, Carolyne; Hinge, Maja; Murphy, Connor S; DeMambro, Victoria; Pettitt, Jessica A; Lary, Christine W; Driscoll, Heather E; McDonald, Michelle M; Kassem, Moustapha; Rosen, Clifford; Andersen, Thomas L.; van Wijnen, Andre J; Jafari, Abbas; Reagan, Michaela R.

In: Cancer Research, Vol. 81, No. 3, 2021, p. 634–647.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fairfield, H, Dudakovic, A, Khatib, CM, Farrell, M, Costa, S, Falank, C, Hinge, M, Murphy, CS, DeMambro, V, Pettitt, JA, Lary, CW, Driscoll, HE, McDonald, MM, Kassem, M, Rosen, C, Andersen, TL, van Wijnen, AJ, Jafari, A & Reagan, MR 2021, 'Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP)', Cancer Research, vol. 81, no. 3, pp. 634–647. https://doi.org/10.1158/0008-5472.CAN-20-1088

APA

Fairfield, H., Dudakovic, A., Khatib, C. M., Farrell, M., Costa, S., Falank, C., Hinge, M., Murphy, C. S., DeMambro, V., Pettitt, J. A., Lary, C. W., Driscoll, H. E., McDonald, M. M., Kassem, M., Rosen, C., Andersen, T. L., van Wijnen, A. J., Jafari, A., & Reagan, M. R. (2021). Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP). Cancer Research, 81(3), 634–647. https://doi.org/10.1158/0008-5472.CAN-20-1088

Vancouver

Fairfield H, Dudakovic A, Khatib CM, Farrell M, Costa S, Falank C et al. Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP). Cancer Research. 2021;81(3):634–647. https://doi.org/10.1158/0008-5472.CAN-20-1088

Author

Fairfield, Heather ; Dudakovic, Amel ; Khatib, Casper M ; Farrell, Mariah ; Costa, Samantha ; Falank, Carolyne ; Hinge, Maja ; Murphy, Connor S ; DeMambro, Victoria ; Pettitt, Jessica A ; Lary, Christine W ; Driscoll, Heather E ; McDonald, Michelle M ; Kassem, Moustapha ; Rosen, Clifford ; Andersen, Thomas L. ; van Wijnen, Andre J ; Jafari, Abbas ; Reagan, Michaela R. / Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP). In: Cancer Research. 2021 ; Vol. 81, No. 3. pp. 634–647.

Bibtex

@article{e8ee29062bc348518c65ddce2b6b28b8,
title = "Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP)",
abstract = "Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity - two key risk factors in multiple myeloma disease prevalence - suggesting that BMAd may influence and be influenced by myeloma cells in the marrow. Here we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAd play a role in multiple myeloma pathogenesis and treatment response. Bone marrow biopsies from MM patients revealed significant loss of BMAT with myeloma cell infiltration of the marrow, whereas BMAT was restored after treatment for multiple myeloma. Myeloma cells reduced BMAT in different pre-clinical murine models of multiple myeloma and in vitro using myeloma cell-adipocyte co-cultures. In addition, multiple myeloma cells altered adipocyte gene expression and cytokine secretory profiles, which were also associated with bioenergetic changes and induction of a senescent-like phenotype. In vivo, senescence markers were also increased in the bone marrow of tumor-burdened mice. BMAd, in turn, provided resistance to dexamethasone-induced cell cycle arrest and apoptosis, illuminating a new possible driver of myeloma cell evolution in a drug resistant clone. Our findings reveal that bi-directional interactions between BMAd and myeloma cells have significant implications for the pathogenesis and treatment of multiple myeloma. Targeting senescence in the bone marrow adipocyte or other bone marrow cells may represent a novel therapeutic approach for treatment of multiple myeloma.",
author = "Heather Fairfield and Amel Dudakovic and Khatib, {Casper M} and Mariah Farrell and Samantha Costa and Carolyne Falank and Maja Hinge and Murphy, {Connor S} and Victoria DeMambro and Pettitt, {Jessica A} and Lary, {Christine W} and Driscoll, {Heather E} and McDonald, {Michelle M} and Moustapha Kassem and Clifford Rosen and Andersen, {Thomas L.} and {van Wijnen}, {Andre J} and Abbas Jafari and Reagan, {Michaela R}",
note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",
year = "2021",
doi = "10.1158/0008-5472.CAN-20-1088",
language = "English",
volume = "81",
pages = "634–647",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "3",

}

RIS

TY - JOUR

T1 - Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP)

AU - Fairfield, Heather

AU - Dudakovic, Amel

AU - Khatib, Casper M

AU - Farrell, Mariah

AU - Costa, Samantha

AU - Falank, Carolyne

AU - Hinge, Maja

AU - Murphy, Connor S

AU - DeMambro, Victoria

AU - Pettitt, Jessica A

AU - Lary, Christine W

AU - Driscoll, Heather E

AU - McDonald, Michelle M

AU - Kassem, Moustapha

AU - Rosen, Clifford

AU - Andersen, Thomas L.

AU - van Wijnen, Andre J

AU - Jafari, Abbas

AU - Reagan, Michaela R

N1 - Copyright ©2020, American Association for Cancer Research.

PY - 2021

Y1 - 2021

N2 - Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity - two key risk factors in multiple myeloma disease prevalence - suggesting that BMAd may influence and be influenced by myeloma cells in the marrow. Here we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAd play a role in multiple myeloma pathogenesis and treatment response. Bone marrow biopsies from MM patients revealed significant loss of BMAT with myeloma cell infiltration of the marrow, whereas BMAT was restored after treatment for multiple myeloma. Myeloma cells reduced BMAT in different pre-clinical murine models of multiple myeloma and in vitro using myeloma cell-adipocyte co-cultures. In addition, multiple myeloma cells altered adipocyte gene expression and cytokine secretory profiles, which were also associated with bioenergetic changes and induction of a senescent-like phenotype. In vivo, senescence markers were also increased in the bone marrow of tumor-burdened mice. BMAd, in turn, provided resistance to dexamethasone-induced cell cycle arrest and apoptosis, illuminating a new possible driver of myeloma cell evolution in a drug resistant clone. Our findings reveal that bi-directional interactions between BMAd and myeloma cells have significant implications for the pathogenesis and treatment of multiple myeloma. Targeting senescence in the bone marrow adipocyte or other bone marrow cells may represent a novel therapeutic approach for treatment of multiple myeloma.

AB - Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity - two key risk factors in multiple myeloma disease prevalence - suggesting that BMAd may influence and be influenced by myeloma cells in the marrow. Here we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAd play a role in multiple myeloma pathogenesis and treatment response. Bone marrow biopsies from MM patients revealed significant loss of BMAT with myeloma cell infiltration of the marrow, whereas BMAT was restored after treatment for multiple myeloma. Myeloma cells reduced BMAT in different pre-clinical murine models of multiple myeloma and in vitro using myeloma cell-adipocyte co-cultures. In addition, multiple myeloma cells altered adipocyte gene expression and cytokine secretory profiles, which were also associated with bioenergetic changes and induction of a senescent-like phenotype. In vivo, senescence markers were also increased in the bone marrow of tumor-burdened mice. BMAd, in turn, provided resistance to dexamethasone-induced cell cycle arrest and apoptosis, illuminating a new possible driver of myeloma cell evolution in a drug resistant clone. Our findings reveal that bi-directional interactions between BMAd and myeloma cells have significant implications for the pathogenesis and treatment of multiple myeloma. Targeting senescence in the bone marrow adipocyte or other bone marrow cells may represent a novel therapeutic approach for treatment of multiple myeloma.

U2 - 10.1158/0008-5472.CAN-20-1088

DO - 10.1158/0008-5472.CAN-20-1088

M3 - Journal article

C2 - 33218968

VL - 81

SP - 634

EP - 647

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 3

ER -

ID: 253401180