Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells

Herroon, Mackenzie K.; Mecca, Shane; Haimbaugh, Alex; Garmo, Laimar C.; Rajagurubandara, Erandi; Todi, Sokol V.; Baker, Tracie R.; Podgorski, Izabela

doi:10.1016/j.bbamcr.2021.119101

Cited by 5 publications

(4 citation statements)

References 94 publications

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“…This was associated with increased hypoxia signaling and activation of pro-survival pathways in PC3 cells. In another study, RNA sequencing analysis showed that exposure to adipocytes controls endoplasmic reticulum (ER) stress and the unfolded protein response signature in metastatic prostate cancer cells, partially through coordination by BIP/HSPA5, an ER chaperone ( 33 ). These findings were consistent with the overexpression of ER stress-associated genes in prostate cancer patients with bone metastasis.…”

Section: Resultsmentioning

confidence: 99%

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review

Salamanna,

Contartese,

Errani

et al. 2023

Front. Endocrinol.

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PurposeBone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.MethodsA comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, to identify studies published from March 2013 to June 2023. Two independent reviewers assessed and screened the literature, extracted the data, and evaluated the quality of the studies. The body of evidence was evaluated and graded using the ROBINS-I tool for non-randomized studies of interventions and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool for in vivo studies. The results were synthesized using descriptive methods.ResultsThe search yielded a total of 463 studies, of which 17 studies were included in the final analysis, including 15 preclinical studies and two non-randomized clinical studies. Analysis of preclinical studies revealed that BMAs play a significant role in bone metastasis, particularly in prostate cancer followed by breast and malignant melanoma cancers. BMAs primarily influence cancer cells by inducing a glycolytic phenotype and releasing or upregulating soluble factors, chemokines, cytokines, adipokines, tumor-derived fatty acid-binding protein (FABP), and members of the nuclear receptor superfamily, such as chemokine (C-C motif) ligand 7 (CCL7), C-X-C Motif Chemokine Ligand (CXCL)1, CXCL2, interleukin (IL)-1β, IL-6, FABP4, and peroxisome proliferator-activated receptor γ (PPARγ). These factors also contribute to adipocyte lipolysis and regulate a pro-inflammatory phenotype in BMAs. However, the number of clinical studies is limited, and definitive conclusions cannot be drawn.ConclusionThe preclinical studies reviewed indicate that BMAs may play a crucial role in bone metastasis in prostate, breast, and malignant melanoma cancers. Nevertheless, further preclinical and clinical studies are needed to better understand the complex role and relationship between BMAs and cancer cells in the bone microenvironment. Targeting BMAs in combination with standard treatments holds promise as a potential therapeutic strategy for bone metastasis.

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Section: Resultsmentioning

confidence: 99%

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review

Salamanna,

Contartese,

Errani

et al. 2023

Front. Endocrinol.

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“…In addition to oxidative stress, two recent studies from Heroon et al. ( 30 , 34 ) have examined the upregulation of markers of endoplasmic reticulum (ER) stress in PCa cells upon interaction with bone marrow adipocytes. Their findings suggest that ER chaperone glucose regulated protein 78 (BIP), may be involved in facilitating bone marrow adipocyte-mediated ER stress in metastatic PCa cells which may help them survive in the bone marrow environment.…”

Section: Prostate Cancermentioning

confidence: 99%

“…Bone is the most common metastatic site in prostate cancer (PCa) (29). Several studies have implicated bone marrow adipocytes as key facilitators of the progression and exacerbation of these bone metastases, as summarized in Figure 1 (30)(31)(32)(33)(34). Two recent preclinical trials have emphasized the association between an increased number bone marrow adipocytes, volume of BMAT and the progression of PCa cells in the bone marrow niche (32,33).…”

Section: Prostate Cancermentioning

confidence: 99%

“…While these data point to antioxidants as a potential strategy for treating bone metastasis in PCa, a recent systematic review indicated that the efficacy of antioxidant supplements taken by cancer patients remains unclear (46). In addition to oxidative stress, two recent studies from Heroon et al (30,34) have examined the upregulation of markers of endoplasmic reticulum (ER) stress in PCa cells upon interaction with bone marrow adipocytes. Their findings suggest that ER chaperone glucose regulated protein 78 (BIP), may be involved in facilitating bone marrow adipocyte-mediated ER stress in metastatic PCa cells which may help them survive in the bone marrow environment.…”

Section: Prostate Cancermentioning

confidence: 99%

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Adipocyte-Cancer Cell Interactions in the Bone Microenvironment

Otley

Sinal

2022

Front. Endocrinol.

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When compared to adipocytes in other anatomical sites, the interaction of bone marrow resident adipocytes with the other cells in their microenvironment is less well understood. Bone marrow adipocytes originate from a resident, self-renewing population of multipotent bone marrow stromal cells which can also give rise to other lineages such as osteoblasts. The differentiation fate of these mesenchymal progenitors can be influenced to favour adipogenesis by several factors, including the administration of thiazolidinediones and increased age. Experimental data suggests that increases in bone marrow adipose tissue volume may make bone both more attractive to metastasis and conducive to cancer cell growth. Bone marrow adipocytes are known to secrete a variety of lipids, cytokines and bioactive signaling molecules known as adipokines, which have been implicated as mediators of the interaction between adipocytes and cancer cells. Recent studies have provided new insight into the impact of bone marrow adipose tissue volume expansion in regard to supporting and exacerbating the effects of bone metastasis from solid tumors, focusing on prostate, breast and lung cancer and blood cancers, focusing on multiple myeloma. In this mini-review, recent research developments pertaining to the role of factors which increase bone marrow adipose tissue volume, as well as the role of adipocyte secreted factors, in the progression of bone metastatic prostate and breast cancer are assessed. In particular, recent findings regarding the complex cross-talk between adipocytes and metastatic cells of both lung and prostate cancer are highlighted.

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Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response

Wilson

Garmo

Podgorski

2022

Pharmacology & Therapeutics

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Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells

Cited by 5 publications

References 94 publications

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review

Adipocyte-Cancer Cell Interactions in the Bone Microenvironment

Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response

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