Interleukin-6 derived from cancer-associated fibroblasts attenuates the p53 response to doxorubicin in prostate cancer cells

Cheteh, Emarndeena H; Sarne, Victoria; Ceder, Sophia; Bianchi, Julie; Augsten, Martin; Rundqvist, Helene; Egevad, Lars; Östman, Arne; Wiman, Klas G.

doi:10.1038/s41420-020-0272-5

Cited by 71 publications

(53 citation statements)

References 64 publications

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“…Moreover, experimental models with CAFs isolated from bone metastases illuminated a role of oncogenic miR-221-containing CAFs microvesicles in inducing hormonal therapy resistance in human BrCa cells, a mechanism that was mainly sustained by autocrine IL-6 signaling [ 137 ]. CAFs-derived IL-6 was further shown to mediate resistance to the cytotoxic effects of doxorubicin in PrCa cells [ 138 ]. These observations may identify CAFs as a promising target in bone-homing malignancies.…”

Section: Impact Of Inflammation On Cancer Metastases To Bonementioning

confidence: 99%

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Göbel

Dell'Endice

Jaschke

et al. 2021

IJMS

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Tumor metastasis to bone is a common event in multiple forms of malignancy. Inflammation holds essential functions in homeostasis as a defense mechanism against infections and is a strategy to repair injured tissue and to adapt to stress conditions. However, exaggerated and/or persistent (chronic) inflammation may eventually become maladaptive and evoke diseases such as autoimmunity, diabetes, inflammatory tissue damage, fibrosis, and cancer. In fact, inflammation is now considered a hallmark of malignancy with prognostic relevance. Emerging studies have revealed a central involvement of inflammation in several steps of the metastatic cascade of bone-homing tumor cells through supporting their survival, migration, invasion, and growth. The mechanisms by which inflammation favors these steps involve activation of epithelial-to-mesenchymal transition (EMT), chemokine-mediated homing of tumor cells, local activation of osteoclastogenesis, and a positive feedback amplification of the protumorigenic inflammation loop between tumor and resident cells. In this review, we summarize established and evolving concepts of inflammation-driven tumorigenesis, with a special focus on bone metastasis.

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Section: Impact Of Inflammation On Cancer Metastases To Bonementioning

confidence: 99%

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Göbel

Dell'Endice

Jaschke

et al. 2021

IJMS

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“…Consistently, the activity of the IL-6/STAT3 signaling pathway is proportional to the growth rate of advanced prostate cancer [ 56 ]. Additionally, it has been found that in LNCAP cells the IL-6-activated JAK/STAT3 pathway also downregulates p53, a major cell cycle regulator [ 57 , 58 ]. Multiple lines of evidence indicate that the CAF-secreted IL-6 may also influence tumor growth by affecting AR activity.…”

Section: Rsv Inhibits Prostate Cancer Cell Proliferation By Targetmentioning

confidence: 99%

The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment

Silk

Reich

Sinha

et al. 2021

JoX

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Prostate cancer is one of the most common cancers diagnosed in men in the United States and the second leading cause of cancer-related deaths worldwide. Since over 60% of prostate cancer cases occur in men over 65 years of age, and this population will increase steadily in the coming years, prostate cancer will be a major cancer-related burden in the foreseeable future. Accumulating data from more recent research suggest that the tumor microenvironment (TME) plays a previously unrecognized role in every stage of cancer development, including initiation, proliferation, and metastasis. Prostate cancer is not only diagnosed in the late stages of life, but also progresses relatively slowly. This makes prostate cancer an ideal model system for exploring the potential of natural products as cancer prevention and/or treatment reagents because they usually act relatively slowly compared to most synthetic drugs. Resveratrol (RSV) is a naturally occurring stilbenoid and possesses strong anti-cancer properties with few adverse effects. Accumulating data from both in vitro and in vivo experiments indicate that RSV can interfere with prostate cancer initiation and progression by targeting the TME. Therefore, this review is aimed to summarize the recent advancement in RSV-inhibited prostate cancer initiation, proliferation, and metastasis as well as the underlying molecular mechanisms, with particular emphasis on the effect of RSV on TME. This will not only better our understanding of prostate cancer TMEs, but also pave the way for the development of RSV as a potential reagent for prostate cancer prevention and/or therapy.

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“…Studies showed that altered p53 function in CAFs contributes to tumor progression 20 . Another study showed that IL-6 secreted from CAFs depletes p53 through STAT3 in prostate cancer cells 21 . Therefore, CAFs serve as a powerful partner for cancer cells, enabling the latter to invade and metastasize to many sites.…”

Section: Effect Of Cdes On Cafsmentioning

confidence: 99%

Concise review: The role of cancer-derived exosomes in tumorigenesis and immune cell modulation

2020

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Exosomes are subcellular entities which were first discovered in the 1980s. Over the past decade, scientists have discovered that they carry components of genetic information that allow for cell-cell communication and cell targeting. Exosomes secreted by cancer cells are termed cancer-derived exosomes (CDEs), and play an important role in tumor formation and progression. Specifically, CDEs mediate the communication between cancer cells, as well as between cancer cells and other cells in the tumor microenvironment, including cancer-associated fibroblasts, endothelial cells, mesenchymal stem cells, and effector immune cells. Additionally, through the vascular system and body fluids, CDEs can modulate response to drugs, increase angiogenesis, stimulate proliferation, promote invasion and metastasis, and facilitate escape from immune surveillance. This review will discuss the relationship between cancer cells and other cells (particularly immune cells), as mediated through CDEs, as well as the subsequent impact on tumorigenesis and immunomodulation. Understanding the role of CDEs in tumorigenesis and immune cell modulation will help advance their utilization in the diagnosis, prognosis, and treatment of cancer.

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Interleukin-6 derived from cancer-associated fibroblasts attenuates the p53 response to doxorubicin in prostate cancer cells

Cited by 71 publications

References 64 publications

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment

Concise review: The role of cancer-derived exosomes in tumorigenesis and immune cell modulation

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