What question did this study set out to answer?

The study investigates how obesity-induced changes in adipose tissue affect ovarian cancer progression via IGF-1 signaling.

April 5, 2026

Abstract 4083: The impact of obesity-induced changes in adipose tissue on ovarian cancer progression

Q: What does this research mean for the field?

High BMI omental preadipocytes enhance early ovarian tumor growth and reduce survival in mice compared to normal BMI preadipocytes, driven by increased IGF-1 secretion and NF-κB signaling. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

High BMI omental preadipocytes enhanced early ovarian tumor growth and reduced survival in mice compared to normal BMI preadipocytes, driven by increased IGF-1 secretion and NF-κB signaling.

Key Points

The study investigates how obesity-induced changes in adipose tissue affect ovarian cancer progression via IGF-1 signaling.
Used in vitro co-culture and in vivo co-injection models with human ovarian cancer cell lines
Compared the effects of omental preadipocytes and mature adipocytes on cancer cell behavior
Assessed IGF-1 secretion and NF-κB signaling dynamics in high and normal BMI preadipocytes
Evaluated tumor growth rates and survival impacts in mouse models
High BMI preadipocytes enhanced early tumor growth and reduced survival in mice compared to normal BMI preadipocytes
Tumors from high BMI showed increased phosphorylation of p65 (Rel A), indicating altered NF-κB signaling
Significant increase in IGF-1 levels from high BMI preadipocytes
Reduced SOX2 expression and increased FN1 levels suggest changes in cancer cell characteristics due to the adipose microenvironment

Structured PICO

Does co-culture or co-injection with high BMI preadipocytes enhance ovarian cancer progression compared to normal BMI preadipocytes?

Population

In vitro co-culture and in vivo co-injection models with human ovarian cancer cell lines and isolated omental preadipocytes from high or normal BMI donors

Intervention

Co-culture or co-injection with isolated omental preadipocytes from high BMI donors

Comparator

Co-culture or co-injection with isolated omental preadipocytes from normal BMI donors

Outcome

Tumor growth and survival of micesurrogate

High BMI omental preadipocytes enhance ovarian cancer progression and reduce survival in preclinical models, potentially driven by IGF-1 mediated NF-κB signaling.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Obesity, characterized by excessive accumulation of body fat, is increasingly prevalent and is recognized as a risk factor for ovarian cancer. Omental adipose tissue is the initial metastatic niche for ovarian cancer cells, providing a conducive microenvironment enriched in fatty acids and cytokines that facilitates tumor migration and proliferation. Elevated NF-κB signaling associated with obesity is well-documented to aberrantly influence cancer cell behavior, potentially enhancing the tumor-supportive characteristics of adipose tissue. Despite this established link, the role of specific adipose cell populations in NF-κB-mediated ovarian cancer metastasis, particularly omental preadipocytes which are progenitors to mature adipocytes, remains unclear. Previous studies in our lab identified Insulin-like growth factor-1 (IGF-1), secreted by preadipocytes, as an activator of NF-κB that promotes extracellular matrix (ECM) remodeling and metastasis. Therefore, we hypothesize that preadipocytes from obese omental tissue contribute to ovarian cancer progression through IGF-1 mediated enrichment of NF-κB signaling. To test this, we used in vitro co-culture and in vivo co-injection models with human ovarian cancer cell lines to compare adipocytes and preadipocytes in supporting ovarian cancer during isolation stress-inducing conditions. Our findings revealed that mature adipocytes and preadipocytes generate tumors and activate NF-κB at similar levels. However, when we compared co-injections of GFP labeled cancer cells with isolated omental preadipocytes from high or normal BMI donors, we found that high BMI preadipocytes enhanced early tumor growth and reduced survival of mice. Tumors from high BMI exhibited increased phosphorylation of p65 (Rel A), suggesting that the obese adipose microenvironment may modulate NF-κB signaling dynamics to support tumor growth. We further assessed SOX2 and FN1 expression in GFP positive sorted cells and found a significant decrease in SOX2 expression and increased FN1 levels, suggesting reduced cancer cell stemness and enhanced proliferative, ECM-remodeling programs. To assess IGF-1 secretion, we utilized co-culture studies and found increased IGF-1 levels from high BMI preadipocytes. Our findings highlight the critical role of obesity-induced alterations in omental adipose tissue, particularly in preadipocytes, with IGF-1 signaling as a key factor that may drive metastasis. Ongoing studies aim to interrogate IGF-1 dependent NF-κB activation for ECM-remodeling and metastatic growth using knockdown models. These results will be further validated in an obesity-induced mouse model to assess whether IGF-1 is required to drive ECM remodeling and metastasis. This study provides valuable insight into how obese adipose tissue influences tumor biology, potentially guiding the development of therapeutic strategies for obese ovarian cancer patients. Citation Format: Sofia Howe, Emily Rodriguez, Mikella Robinson, Carrie Danielle House. The impact of obesity-induced changes in adipose tissue on ovarian cancer progression abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4083.

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