Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

Herroon, Mackenzie K.; Rajagurubandara, Erandi; Hardaway, Aimalie; Powell, Katelyn; Turchick, Audrey; Feldmann, Daniel P.; Podgorski, Izabela

doi:10.18632/oncotarget.1482

Cited by 168 publications

(261 citation statements)

References 68 publications

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“…34 In addition, this CM enhanced the proliferation and invasion of PC3 cells in vitro, whereas inhibitors of FABP4 and IL-1b prevented invasion. 34 Interestingly, in an in vivo study, the increase of FABP4, IL-1b and HMOX-1 genes was observed in tumors within the marrow, but not in tumors grown subcutaneously. 34 Consistent with this, high levels of FABP4 expression are observed in human bone metastatic tumors near adipocytes.…”

Section: Adipocytesmentioning

confidence: 90%

“…34 Interestingly, in an in vivo study, the increase of FABP4, IL-1b and HMOX-1 genes was observed in tumors within the marrow, but not in tumors grown subcutaneously. 34 Consistent with this, high levels of FABP4 expression are observed in human bone metastatic tumors near adipocytes. 34 Of added interest, aside from metabolic dysfunction, daily dietary intake may also alter the effects of adipocytes on metastatic niche development.…”

Section: Adipocytesmentioning

confidence: 95%

“…Adipocytes are known to be involved in tumor progression and metastasis, 32,33 which may be partly owing to their negative effects on hematopoiesis; 13 however, little is known regarding the specific roles that these cells have in the metastatic process. A recent study demonstrated that marrow adipocytes support bone metastasis of prostate cancer, 34 as more PC3 cells, a prostate cancer cell line, grew in the bone marrow of animals receiving a high-fat diet than in that of animals on a regular diet. 34 Conditioned medium (CM) from adipocyte lineage cultures were obtained from differentiated mouse bone marrow stromal cells and found to increase gene expression of fatty acid binding protein 4 (FABP4), interleukin (IL)-1b and heme oxygenase (decycling) 1 (HMOX-1) in PC3 cells in vitro; however, this could be stopped by PPAR g inhibitors.…”

Section: Adipocytesmentioning

confidence: 99%

“…A recent study demonstrated that marrow adipocytes support bone metastasis of prostate cancer, 34 as more PC3 cells, a prostate cancer cell line, grew in the bone marrow of animals receiving a high-fat diet than in that of animals on a regular diet. 34 Conditioned medium (CM) from adipocyte lineage cultures were obtained from differentiated mouse bone marrow stromal cells and found to increase gene expression of fatty acid binding protein 4 (FABP4), interleukin (IL)-1b and heme oxygenase (decycling) 1 (HMOX-1) in PC3 cells in vitro; however, this could be stopped by PPAR g inhibitors. 34 In addition, this CM enhanced the proliferation and invasion of PC3 cells in vitro, whereas inhibitors of FABP4 and IL-1b prevented invasion.…”

Section: Adipocytesmentioning

confidence: 99%

“…34 Conditioned medium (CM) from adipocyte lineage cultures were obtained from differentiated mouse bone marrow stromal cells and found to increase gene expression of fatty acid binding protein 4 (FABP4), interleukin (IL)-1b and heme oxygenase (decycling) 1 (HMOX-1) in PC3 cells in vitro; however, this could be stopped by PPAR g inhibitors. 34 In addition, this CM enhanced the proliferation and invasion of PC3 cells in vitro, whereas inhibitors of FABP4 and IL-1b prevented invasion. 34 Interestingly, in an in vivo study, the increase of FABP4, IL-1b and HMOX-1 genes was observed in tumors within the marrow, but not in tumors grown subcutaneously.…”

Section: Adipocytesmentioning

confidence: 99%

See 4 more Smart Citations

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

Shiozawa¹,

Eber²,

Berry³

et al. 2015

BoneKEy Reports

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Bone marrow is a heterogeneous organ containing diverse cell types, and it is a preferred metastatic site for several solid tumors such as breast and prostate cancer. Recently, it has been shown that bone metastatic cancer cells interact with the bone marrow microenvironment to survive and grow, and thus this microenvironment is referred to as the 'metastatic niche'. Once cancer cells spread to distant organs such as bone, the prognosis for the patient is generally poor. There is an urgent need to establish a greater understanding of the mechanisms whereby the bone marrow niche influences bone metastasis. Here we discuss insights into the contribution of the bone marrow 'metastatic niche' to progression of bone metastatic disease, with a particular focus on cells of hematopoietic and mesenchymal origin.

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Section: Adipocytesmentioning

confidence: 90%

Section: Adipocytesmentioning

confidence: 95%

Section: Adipocytesmentioning

confidence: 99%

Section: Adipocytesmentioning

confidence: 99%

Section: Adipocytesmentioning

confidence: 99%

See 3 more Smart Citations

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

Shiozawa¹,

Eber²,

Berry³

et al. 2015

BoneKEy Reports

View full text Add to dashboard Cite

show abstract

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

et al. 2020

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Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid-binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial-to-mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid b-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARc activation which, in turn, regulates FABP12's role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP-PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

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GelMA and Biomimetic Culture Allow the Engineering of Mineralized, Adipose, and Tumor Tissue Human Microenvironments for the Study of Advanced Prostate Cancer In Vitro and In Vivo

Bessot

Gunter

Waugh

et al. 2023

Adv Healthcare Materials

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Increasing evidence shows bone marrow (BM)‐adipocytes as a potentially important contributor in prostate cancer (PCa) bone metastases. However, a lack of relevant models has prevented the full understanding of the effects of human BM‐adipocytes in this microenvironment. It is hypothesized that the combination of tunable gelatin methacrylamide (GelMA)‐based hydrogels with the biomimetic culture of human cells would offer a versatile 3D platform to engineer human bone tumor microenvironments containing BM‐adipocytes. Human osteoprogenitors, adipocytes, and PCa cells are individually cultured in vitro in GelMA hydrogels, leading to mineralized, adipose, and PCa tumor 3D microtissues, respectively. Osteoblast mineralization and tumor spheroid formation are tailored by hydrogel stiffness with lower stiffnesses correlating with increased mineralization and tumor spheroid size. Upon coculture with tumor cells, BM‐adipocytes undergo morphological changes and delipidation, suggesting reciprocal interactions between the cell types. When brought in vivo, the mineralized and adipose microtissues successfully form a humanized fatty bone microenvironment, presenting, for the first time, with human adipocytes. Using this model, an increase in tumor burden is observed when human adipocytes are present, suggesting that adipocytes support early bone tumor growth. The advanced platform presented here combines natural aspects of the microenvironment with tunable properties useful for bone tumor research.

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Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

Cited by 168 publications

References 68 publications

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

The FABP12/PPARγ pathway promotes metastatic transformation by inducing epithelial‐to‐mesenchymal transition and lipid‐derived energy production in prostate cancer cells

GelMA and Biomimetic Culture Allow the Engineering of Mineralized, Adipose, and Tumor Tissue Human Microenvironments for the Study of Advanced Prostate Cancer In Vitro and In Vivo

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