Regulatory Role of the Adipose Microenvironment on Ovarian Cancer Progression

Chehade, Hussein; Tedja, Roslyn; Ramos, Harry; Bawa, Tejeshwar; Adzibolosu, Nicholas; Gogoi, Radhika; Mor, Gil; Alvero, Ayesha B.

doi:10.3390/cancers14092267

Cited by 14 publications

(8 citation statements)

References 126 publications

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“…The inclination of this preference for adipose tissue is believed to be rooted in the release of adipokines from the omentum, which, in turn, promotes cancer-associated characteristics by supplying energy from adipocytes to cancer cells [ 13 ]. In the context of chemoresistance, lipids or their regulatory factors derived from adipose tissues have been reported to affect the survival of ovarian cancer cells, as well as influencing proliferation or metastasis [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer

Kim,

Jung

2024

Biomedicines

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Obesity is recognized as a significant risk factor for ovarian cancer, with accumulating evidence highlighting its impact on disease progression and chemoresistance. This review synthesizes current research elucidating the link between obesity-induced lysosomal dysfunction and ovarian cancer chemoresistance. Epidemiological studies consistently demonstrate a positive correlation between body mass index (BMI) and ovarian cancer risk, attributed in part to the predilection of epithelial ovarian cancer cells for adipose tissue, particularly the omentum. Adipokines released from the omentum contribute to cancer-associated characteristics, including energy supply to cancer cells. Moreover, obesity-induced alterations in lysosomal function have been implicated in systemic inflammation and lipid metabolism dysregulation, further exacerbating cancer progression. Lysosomes play a crucial role in drug resistance, as evidenced by studies demonstrating their involvement in mediating resistance to chemotherapy in ovarian cancer cells. Recent findings suggest that pharmacological inhibition of lysosomal calcium channels sensitizes drug-resistant ovarian cancer cells to cisplatin treatment, highlighting the therapeutic potential of targeting lysosomal dysfunction in obesity-related chemoresistance. This review underscores the importance of understanding the multifaceted roles of lysosomes in obesity-related drug resistance and their implications for the development of targeted therapeutic interventions in ovarian cancer management.

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Section: Introductionmentioning

confidence: 99%

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer

Kim,

Jung

2024

Biomedicines

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“…In addition, changes in the TME affect cell status and further drive drug responses. Currently, the influence of adipocytes, the primary component of ARM, on chemoresistance in EOC has raised concerns ( 1 , 15 , 16 ). Adipocytes also secrete certain adipokines, including leptin, visfatin, resistin and adiponectin, amongst other factors, to induce drug resistance ( 1 , 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, the influence of adipocytes, the primary component of ARM, on chemoresistance in EOC has raised concerns ( 1 , 15 , 16 ). Adipocytes also secrete certain adipokines, including leptin, visfatin, resistin and adiponectin, amongst other factors, to induce drug resistance ( 1 , 15 , 16 ). However, little is known regarding the mechanisms involved in the contribution of ARM to chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

Adipocyte‑rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator‑activated receptor gamma/ABCG2 in epithelial ovarian cancer

Chen,

Liu,

et al. 2024

Int J Mol Med

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The effects of adipocyte-rich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyte-rich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARM-associated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro . Specifically, the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3-shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARM-educated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.

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“…In ovarian cancer, the process of metastasis has been divided into 3 sequential steps: detachment from primary tumor, transit, and attachment/colonization of secondary sites [ 8 , 12 , 13 ]. In the first step, ovarian cancer cells can detach passively from the primary tumor by sloughing off as a result of mechanical forces from the peritoneal fluid, or actively, by initiating an EMT program [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%