Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer

Joakin O. Mori; Isra Elhussin; W. Nathaniel Brennen; Mindy K. Graham; Tamara L. Lotan; Clayton C. Yates; Angelo M. De Marzo; Samuel R. Denmeade; Srinivasan Yegnasubramanian; William G. Nelson; Gerald V. Denis; Elizabeth A. Platz; Alan K. Meeker; Christopher M. Heaphy

doi:10.1038/s41585-023-00827-x

Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer

Joakin O. Mori, Isra Elhussin, W. Nathaniel Brennen, Mindy K. Graham, Tamara L. Lotan, Clayton C. Yates, Angelo M. De Marzo, Samuel R. Denmeade, Srinivasan Yegnasubramanian, William G. Nelson, Gerald V. Denis, Elizabeth A. Platz, Alan K. Meeker, Christopher M. Heaphy

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

Abstract

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

Original language	English (US)
Pages (from-to)	258-273
Number of pages	16
Journal	Nature Reviews Urology
Volume	21
Issue number	5
DOIs	https://doi.org/10.1038/s41585-023-00827-x
State	Published - May 2024

ASJC Scopus subject areas

Urology

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Mori, J. O., Elhussin, I., Brennen, W. N., Graham, M. K., Lotan, T. L., Yates, C. C., De Marzo, A. M., Denmeade, S. R., Yegnasubramanian, S., Nelson, W. G., Denis, G. V., Platz, E. A., Meeker, A. K., & Heaphy, C. M. (2024). Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer. Nature Reviews Urology, 21(5), 258-273. https://doi.org/10.1038/s41585-023-00827-x

Mori, JO, Elhussin, I, Brennen, WN, Graham, MK, Lotan, TL , Yates, CC , De Marzo, AM , Denmeade, SR , Yegnasubramanian, S , Nelson, WG, Denis, GV, Platz, EA , Meeker, AK & Heaphy, CM 2024, 'Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer', Nature Reviews Urology, vol. 21, no. 5, pp. 258-273. https://doi.org/10.1038/s41585-023-00827-x

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title = "Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer",

abstract = "The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.",

author = "Mori, {Joakin O.} and Isra Elhussin and Brennen, {W. Nathaniel} and Graham, {Mindy K.} and Lotan, {Tamara L.} and Yates, {Clayton C.} and {De Marzo}, {Angelo M.} and Denmeade, {Samuel R.} and Srinivasan Yegnasubramanian and Nelson, {William G.} and Denis, {Gerald V.} and Platz, {Elizabeth A.} and Meeker, {Alan K.} and Heaphy, {Christopher M.}",

note = "Publisher Copyright: {\textcopyright} Springer Nature Limited 2023.",

year = "2024",

month = may,

doi = "10.1038/s41585-023-00827-x",

language = "English (US)",

volume = "21",

pages = "258--273",

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AU - Mori, Joakin O.

AU - Elhussin, Isra

AU - Brennen, W. Nathaniel

AU - Graham, Mindy K.

AU - Lotan, Tamara L.

AU - Yates, Clayton C.

AU - De Marzo, Angelo M.

AU - Denmeade, Samuel R.

AU - Yegnasubramanian, Srinivasan

AU - Nelson, William G.

AU - Denis, Gerald V.

AU - Platz, Elizabeth A.

AU - Meeker, Alan K.

AU - Heaphy, Christopher M.

PY - 2024/5

Y1 - 2024/5

N2 - The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

AB - The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

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JF - Nature Reviews Urology

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Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer

Abstract

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