Modeling Human Cancer-induced Cachexia

Erin E. Talbert; Maria C. Cuitiño; Katherine J. Ladner; Priyani V. Rajasekerea; Melissa Siebert; R. Shakya; Gustavo W. Leone; Michael C. Ostrowski; B. Paleo; Noah Weisleder; Peter J. Reiser; Amy Webb; Cynthia D. Timmers; Daniel S. Eiferman; David C. Evans; Mary E. Dillhoff; Carl R. Schmidt; Denis C. Guttridge

doi:10.1016/j.celrep.2019.07.016

Modeling Human Cancer-induced Cachexia

Erin E. Talbert
, Maria C. Cuitiño
, Katherine J. Ladner
, Priyani V. Rajasekerea
, Melissa Siebert
, R. Shakya
, Gustavo W. Leone
, Michael C. Ostrowski
, B. Paleo
, Noah Weisleder
, Peter J. Reiser
, Amy Webb
, Cynthia D. Timmers
, Daniel S. Eiferman
, David C. Evans
, Mary E. Dillhoff
, Carl R. Schmidt
, Denis C. Guttridge

Producción científica: Article › revisión exhaustiva

117 Citas (Scopus)

Resumen

Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia. Talbert et al. developed an inducible mouse model of cachexia caused by pancreatic cancer. This model exhibits features of the human condition, including the progressive depletion of muscle and adipose tissue associated with tumor progression.

Idioma original	English
Páginas (desde-hasta)	1612-1622.e4
Publicación	Cell Reports
Volumen	28
N.º	6
DOI	https://doi.org/10.1016/j.celrep.2019.07.016
Estado	Published - ago 6 2019

Nota bibliográfica

Publisher Copyright:
© 2019 The Authors

Financiación

The authors would like to thank David Wang and Nivedita Ratman for thoughtful discussions of the manuscript, Lisa Baer for assistance with CLAMS; Tom Liu for assistance with the RNA-seq; Sabahattin Bicer for assistance with the myofilament gels; Jason Bice, Daphne Bryant, Raleigh Kladeny, and Melodie Parrish for histology assistance; Ericka Haverick, Karina Woodward, Angela Sarna, and Erica Williams for coordination of human subjects; and Jeffrey Chakedis, Heather Lewis, and Mitchell Ramsey for clinical data extraction. Funding was provided by NIH R21AR071021 (to D.C.G.), R01CA180057 (to D.C.G.), and K99AR071508 (to E.E.T.); and American Cancer Society postdoctoral fellowship PF-15-156-01-CSM (to E.E.T.) and a Weiss postdoctoral fellowship (to E.E.T.). Additional support was from The Ohio State Comprehensive Cancer Center P30CA016058 , OSUCCC institutional funds and Hollings Cancer Center P30CA138313 . A portion of this work was conducted in a facility constructed with support from NIH C06 RR015455 . The authors would like to thank David Wang and Nivedita Ratman for thoughtful discussions of the manuscript, Lisa Baer for assistance with CLAMS; Tom Liu for assistance with the RNA-seq; Sabahattin Bicer for assistance with the myofilament gels; Jason Bice, Daphne Bryant, Raleigh Kladeny, and Melodie Parrish for histology assistance; Ericka Haverick, Karina Woodward, Angela Sarna, and Erica Williams for coordination of human subjects; and Jeffrey Chakedis, Heather Lewis, and Mitchell Ramsey for clinical data extraction. Funding was provided by NIH R21AR071021 (to D.C.G.), R01CA180057 (to D.C.G.), and K99AR071508 (to E.E.T.); and American Cancer Society postdoctoral fellowship PF-15-156-01-CSM (to E.E.T.) and a Weiss postdoctoral fellowship (to E.E.T.). Additional support was from The Ohio State Comprehensive Cancer Center P30CA016058, OSUCCC institutional funds and Hollings Cancer Center P30CA138313. A portion of this work was conducted in a facility constructed with support from NIH C06 RR015455. Conceptualization, E.E.T. and D.C.G.; Formal Analysis, E.E.T. M.C.C. and A.W.; Investigation E.E.T. M.C.C. K.J.L. P.V.R. M.S. B.P. and P.J.R.; Resources, R.S. D.S.E. D.C.E. M.E.D. and C.R.S.; Data Curation, E.E.T. and P.V.R.; Writing?Original Draft, E.E.T. and D.C.G.; Writing?Review & Editing, E.E.T. M.C.C. K.J.L. P.V.R. M.S. R.S. G.W.L. M.C.O. B.P. N.W. P.J.R. A.W. C.D.T, D.S.E. D.C.E. M.E.D. C.R.S. and D.C.G.; Visualization, E.E.T. and D.C.G. Supervision E.E.T. G.W.L. M.C.O. N.W. C.D.T. and D.C.G.; Funding Acquisition, E.E.T. and D.C.G. The authors declare no competing interests.

Financiadores	Número del financiador
E.E.T. M.C.C.
Hollings Cancer Center’s Cancer Center	P30CA138313, C06 RR015455
Ohio State University Comprehensive Cancer Center	P30CA016058
National Institutes of Health (NIH)	R21AR071021, K99AR071508, R01CA180057
American Cancer Society-Michigan Cancer Research Fund	PF-15-156-01-CSM
National Childhood Cancer Registry – National Cancer Institute	R01CA098466

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Acceder al documento

10.1016/j.celrep.2019.07.016

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Talbert, E. E., Cuitiño, M. C., Ladner, K. J., Rajasekerea, P. V., Siebert, M., Shakya, R., Leone, G. W., Ostrowski, M. C., Paleo, B., Weisleder, N., Reiser, P. J., Webb, A., Timmers, C. D., Eiferman, D. S., Evans, D. C., Dillhoff, M. E., Schmidt, C. R., & Guttridge, D. C. (2019). Modeling Human Cancer-induced Cachexia. Cell Reports, 28(6), 1612-1622.e4. https://doi.org/10.1016/j.celrep.2019.07.016

@article{6f8b500b348447559a075d4522a67ed7,

title = "Modeling Human Cancer-induced Cachexia",

abstract = "Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia. Talbert et al. developed an inducible mouse model of cachexia caused by pancreatic cancer. This model exhibits features of the human condition, including the progressive depletion of muscle and adipose tissue associated with tumor progression.",

keywords = "adipose, cachexia, pancreatic cancer, skeletal muscle, wasting, weight loss",

author = "Talbert, \{Erin E.\} and Cuiti{\~n}o, \{Maria C.\} and Ladner, \{Katherine J.\} and Rajasekerea, \{Priyani V.\} and Melissa Siebert and R. Shakya and Leone, \{Gustavo W.\} and Ostrowski, \{Michael C.\} and B. Paleo and Noah Weisleder and Reiser, \{Peter J.\} and Amy Webb and Timmers, \{Cynthia D.\} and Eiferman, \{Daniel S.\} and Evans, \{David C.\} and Dillhoff, \{Mary E.\} and Schmidt, \{Carl R.\} and Guttridge, \{Denis C.\}",

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month = aug,

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doi = "10.1016/j.celrep.2019.07.016",

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Talbert, EE, Cuitiño, MC, Ladner, KJ, Rajasekerea, PV, Siebert, M, Shakya, R, Leone, GW, Ostrowski, MC, Paleo, B, Weisleder, N, Reiser, PJ, Webb, A, Timmers, CD, Eiferman, DS, Evans, DC, Dillhoff, ME, Schmidt, CR & Guttridge, DC 2019, 'Modeling Human Cancer-induced Cachexia', Cell Reports, vol. 28, n.º 6, pp. 1612-1622.e4. https://doi.org/10.1016/j.celrep.2019.07.016

TY - JOUR

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AU - Talbert, Erin E.

AU - Cuitiño, Maria C.

AU - Ladner, Katherine J.

AU - Rajasekerea, Priyani V.

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AU - Shakya, R.

AU - Leone, Gustavo W.

AU - Ostrowski, Michael C.

AU - Paleo, B.

AU - Weisleder, Noah

AU - Reiser, Peter J.

AU - Webb, Amy

AU - Timmers, Cynthia D.

AU - Eiferman, Daniel S.

AU - Evans, David C.

AU - Dillhoff, Mary E.

AU - Schmidt, Carl R.

AU - Guttridge, Denis C.

PY - 2019/8/6

Y1 - 2019/8/6

N2 - Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia. Talbert et al. developed an inducible mouse model of cachexia caused by pancreatic cancer. This model exhibits features of the human condition, including the progressive depletion of muscle and adipose tissue associated with tumor progression.

AB - Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia. Talbert et al. developed an inducible mouse model of cachexia caused by pancreatic cancer. This model exhibits features of the human condition, including the progressive depletion of muscle and adipose tissue associated with tumor progression.

KW - adipose

KW - cachexia

KW - pancreatic cancer

KW - skeletal muscle

KW - wasting

KW - weight loss

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SN - 2211-1247

VL - 28

SP - 1612-1622.e4

JO - Cell Reports

JF - Cell Reports

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ER -

Modeling Human Cancer-induced Cachexia

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

Acceder al documento

Otros archivos y enlaces

Huella

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