Direct evidence of lipid translocation between adipocytes and prostate cancer cells with imaging FTIR microspectroscopy

Gazi, Ehsan; Gardner, Peter; Lockyer, Nicholas P.; Hart, Claire A.; Brown, Michael D.; Clarke, Noel W.

doi:10.1194/jlr.m700131-jlr200

Cited by 140 publications

(123 citation statements)

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“…In long-term human BMS/CaP models malignant cells migrate towards BM-Ad and take up lipids from adipocytes or the surrounding microenvironment (Brown et al, 2006). Separate studies by Tokuda et al (2003) and Gazi et al (2007) found that PC-3 cells interacted directly with adipocytes and using Fourier Transform Infrared spectroscopy (FTIR) to follow deuterated palmitic acid, Gazi et al (2007) confirmed the direct uptake of lipid by CaP cells from BM-Ad.…”

mentioning

confidence: 70%

“…Therefore, as BM-Ads are integrally involved in haematopoietic cell proliferation/propagation, they may also be an important component in CaP -BMS interaction. This may explain the co-localisation of CaP cells with adipocytes and the consequent influence on CaP migration and growth in vitro (Tokuda et al, 2003;Brown et al, 2006;Gazi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…This may be because of human aspirates already containing greater numbers of adipocyte precursors (unlike MSC systems, where adipocyte precursors must undergo adipogenic differentiation) and/or to the long-term BM culture media containing selected FCS and horse serum, which support adipogenesis/haematopoiesis. To assess the effect of specific PUFAs on BM-MSC adipogenesis, we utilised BSCM supplemented with hydrocortisone (an essential factor for inducing adipogenesis within BMS cultures), which we have shown previously to be capable of deriving BM-Ad containing specific fatty acids (Gazi et al, 2007). We now show for the first time that specific lipids have differential effects on adipocyte differentiation in human BMS.…”

Section: Discussionmentioning

confidence: 99%

“…Mesenchymal stem cells were isolated from human donor red cellenriched rib bone marrow using the RosetteSep human MSC enrichment cocktail and cultured as defined by Gazi et al (2007). Briefly, human donor red cell-enriched rib bone marrow was incubated with RosetteSep antibody cocktail (50 mg ml À1 ) for 20 min at room temperature.…”

Section: Mesenchymal Separation From Normal Ribmentioning

confidence: 99%

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Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

et al. 2009

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Royal Hope NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK BACKGROUND: Prostate cancer (CaP) preferentially metastasises to the bone, and we have previously shown that the poly-unsaturated fatty acid (PUFA) arachidonic acid (AA) is a potent stimulator of CaP invasion. Here we present that AA promotes CaP invasion by inducing bone marrow adipocyte formation. METHODS: Boyden invasion-chamber assays assessed the ability of dietary oils, their PUFA components, and specific PUFA-loaded adipocytes to induce PC-3 invasion. Lipid transfer and metabolism was followed using deuterated AA and Fourier Transform Infrared spectroscopy (FTIR). RESULTS: Poly-unsaturated fatty acid constituents, but not their corresponding dietary oils, induced PC-3 invasion. PUFAs induce bone marrow adipocyte (BM-Ad) differentiation with AA inducing higher levels of BM-Ad differentiation, as compared with other PUFAs (3998 ± 514.4 vs 932 ± 265.8; P ¼ 0.00002), which stimulated greater PC-3 invasion than free AA (22 408.5 ± 607.4 vs 16 236±313.9; P ¼ 0.01111) or adipocytes generated in the presence of other PUFAs. In bone marrow co-culture PC-3 and BM-Ad interactions result in direct uptake and metabolism of AA by PC-3 cells, destruction of the adipocyte and subsequent formation of a bone metastasis. CONCLUSION: The data supports the hypothesis that AA not only promotes CaP invasion, it also prepares the 'soil', making it more supportive for implantation and propagation of the migrating metastatic cell.

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mentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mesenchymal Separation From Normal Ribmentioning

confidence: 99%

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Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

et al. 2009

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“…Un tel transfert de lipides entre adipocytes et cellules cancéreuses a également été montré dans le cas de cellules tumorales de prostate [29], mais aussi dans le cancer du sein (données non publiées de notre équipe). L'ensemble de ces résultats montrent qu'un dialogue complexe s'établit entre les adipocytes matures, la tumeur, mais aussi les autres composants du microenvironnement pour favoriser la croissance et la dissémination de la tumeur.…”

Section: Le Tissu Adipeux Ou Plutôt Les Tissus Adipeux : De L'importaunclassified

Tissu adipeux et cancer

et al. 2014

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> Le tissu adipeux est fréquemment retrouvé à proximité des cancers invasifs, en particulier dans le cancer du sein. Parmi les cellules qui le composent, les adipocytes matures, du fait de leur activité sécrétoire, sont hautement susceptibles d'influencer l'agressivité tumorale. Après avoir montré au lecteur les différences fonctionnelles qui existent entre les dépôts du tissu adipeux selon leur localisation anatomique, nous décrirons les modifications phénotypiques spécifiques des adipocytes entourant les tumeurs, cellules que nous avons appelées CAA pour cancerassociated adipocytes. Les CAA, via la sécrétion de cytokines pro-inflammatoires, de protéines de la matrice extracellulaire et le remodelage de cette dernière, ainsi que via la libération d'acides gras libres, stimulent la progression tumorale et la résistance aux traitements. Un dialogue bidirectionnel s'établit donc entre adipocytes et tumeur, dialogue qui pourrait être amplifié dans des conditions d'obésité et, ainsi, expliquer le mauvais pronostic observé chez ces patients. < croissance et la dissémination de la tumeur. L'importance dans ce processus des fibroblastes associés au cancer (CAF pour cancer-associated fibroblast) ou encore des macrophages (TAM pour tumor-associated macrophage) a été clairement décrite [2,3]. Les cellules qui composent le tissu adipeu sont aussi fréquemment retrouvées à proximité des tumeurs, en particulier dans le cancer du sein où elles sont un des composants majoritaires du stroma tumoral. Leur rôle a été longtemps ignoré, mais l'augmentation du nombre d'études les concernant souligne l'intérêt croissant de la communauté scientifique pour cette nouvelle facette du micro-environnement tumoral. Pourquoi s'intéresser au tissu adipeux et, plus particulièrement, aux adipocytes matures ? Ces dernières années, il a été montré que les adipocytes n'étaient pas de simples réservoirs d'énergie, mais des cellules endocrines capables de sécréter une grande variété de molécules (appelées adipokines), incluant des hormones, des facteurs de croissance, des chimiokines ou des molécules pro-inflammatoires, sécrétions dont le profil est modifié dans des conditions d'obésité [4]. Ce profil sécré-toire fait donc des adipocytes d'excellents candidats pour influencer le comportement des tumeurs. Le lien clairement établi entre obésité et cancer renforce l'intérêt d'étudier le rôle des adipocytes matures dans la progression tumorale. En effet, des études épidémiologiques ont maintenant montré de façon convaincante que l'obésité est associée à une augmentation de la mortalité par cancer [5]. Ces données ont des conséquences majeures en termes de santé publique, puisque le surpoids et l'obésité sont en augmentation constante dans le monde, et que leur prévalence atteint maintenant des dimensions alarmantes. En effet, l'Organisation mondiale de la santé prévoit qu'en 2015, trois milliards d'adultes dans le monde seront en surpoids, et 700 millions seront

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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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Direct evidence of lipid translocation between adipocytes and prostate cancer cells with imaging FTIR microspectroscopy

Cited by 140 publications

References 26 publications

Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer

Tissu adipeux et cancer

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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