# Impact of vitamin D on the progression of breast cancer in the case of obesity: a 3D coculture model

Jessy Aoun, Habanjar Ola, Rawan Nehme, Caroline Decombat, Diab-Assaf

Mona, Florence Caldefie-Chezet, Laetitia Delort

► To cite this version:

Jessy Aoun, Habanjar Ola, Rawan Nehme, Caroline Decombat, Diab-Assaf Mona, et al. Impact of vitamin D on the progression of breast cancer in the case of obesity: a 3D coculture model. 46th ESPEN Congress on Clinical Nutrition and Metabolism, Sep 2024, Milan, Italy. hal-04843711

HAL Id: hal-04843711

https://hal.science/hal-04843711v1

Submitted on 17 Dec 2024

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# 46th ESPEN Congress

on Clinical Nutrition & Metabolism
Milan, Italy • 7-10 September 2024

CLINICAL NUTRITION: "THE" TRANSVERSAL SCIENCE

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## IMPACT OF VITAMIN D ON THE PROGRESSION OF BREAST CANCER IN THE CASE OF OBESITY:
A 3D COCULTURE MODEL

AOUN Jessy ¹, HABANJAR Ola¹, NEHME Rawan¹, DECOMBAT Caroline¹, DIAB-ASSAF Mona², CALDEFIE-CHEZET Florence ¹, DELORT Laetitia ¹

1 Clermont-Auvergne University, INRAE, UNH, Clermont-Ferrand, France

2 Lebanese University, Equipe Tumorigénèse Pharmacologie Moléculaire et Anticancéreuse, Fanar, Lebanon

P147

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### Background

The tumor microenvironment is composed of adipose tissue containing macrophages and adipose cells. In obesity, the percentage of resident macrophages increases and becomes M1-like pro-inflammatory macrophages. Adipose cells are preadipocytes that can differentiate into mature adipocytes. In obesity, a hyperplasia and hypertrophy of adipose cells are observed. On the other hand, Vitamin D can act on different cell types in the tumor microenvironment including cancer cells. Obese people are more likely deficient in vitamin D which puts them at higher risk of developing breast cancer. Thus, our objective was to evaluate the effects of vitamin D on the progression of breast cancer in the context of obesity through a 3D co-culture model.

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### Method

#### 1. Formation of spheroids

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Spheroids of adipose
cells (preadipocytes or
mature adipocytes)

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Spheroids of breast
cancer cells

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INCUCYTE®

The formation of spheroids
were monitored by an real-time
tracking system (Incucyte)

#### 2. Polarization of macrophages

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THP1 monocytic
cell line

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72h

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M0 macrophages

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24h

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M1 pro-inflammatory
macrophages

#### 3. Co-culture model

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A co-culture model was developed with 1/ spheroids of preadipocytes or mature adipocytes, 2/ breast cancer cell spheroids in agarose molds, 3/ M1-like macrophages placed at the bottom of a 6-well plate. After 72 hours of treatment with a physiological dose of vit D, RT-qPCR was conducted on the different cell types.

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### Results

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In the coculture with preadipospheroids, Vit D reduced the differentiation of preadipocytes, the inflammation of M1 type macrophages and the proliferation of cancer cells.

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Without vit D

With vit D

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In the coculture with adipospheroids, Vit D increased the expression of leptin in adipospheroids, increased inflammation in M1-type macrophages and had no effect on the proliferation of cancer cells.

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### Summary/ Highlights

Vitamin D, at a physiological level, can reduce inflammation by reducing differentiation of preadipocytes into mature adipocytes and by reducing inflammation in macrophages of adipose tissue while not having an effect with mature adipocytes.

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ESPEN
The European Society for
Clinical Nutrition and Metabolism

## 46th ESPEN Congress

on Clinical Nutrition & Metabolism
Milan, Italy • 7-10 September 2024

CLINICAL NUTRITION: "THE" TRANSVERSAL SCIENCE

### Contact information

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Jessy Aoun

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Jessy.AOUN@uca.fr

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UNIVERSITÉ
Clermont Auvergne