Cancer cell migration depends on adjacent ASC and adipose spheroids in a 3D bioprinted breast cancer model.
Hannes HorderDavid BöhringerNadine EndrizziLaura S HildebrandAlessandro CianciosiSabrina StecherFranziska DusiSophie SchweinitzerMartin WatzlingJuergen GrollJürgen GrollJoerg TessmarPetra Bauer-KreiselBen FabryTorsten BlunkPublished in: Biofabrication (2024)
Breast cancer develops in close proximity to mammary adipose tissue and interactions with the local adipose environment have been shown to drive tumor progression. The specific role, however, of this complex tumor microenvironment in cancer cell migration still needs to be elucidated. Therefore, in this study, a 3D bioprinted breast cancer model was developed that allows for a comprehensive analysis of individual tumor cell migration parameters in dependence of adjacent adipose stroma. In this co-culture model, a breast cancer compartment with MDA-MB-231 breast cancer cells embedded in collagen is surrounded by an adipose tissue compartment consisting of adipose-derived stromal cell (ASC) or adipose spheroids in a printable bioink based on thiolated hyaluronic acid. Printing parameters were optimized for adipose spheroids to ensure viability and integrity of the fragile lipid-laden cells. Preservation of the adipogenic phenotype after printing was demonstrated by quantification of lipid content, expression of adipogenic marker genes, the presence of a coherent adipo-specific extracellular matrix, and cytokine secretion. The migration of tumor cells as a function of paracrine signaling of the surrounding adipose compartment was then analyzed using live-cell imaging. The presence of ASC or adipose spheroids substantially increased key migration parameters of MDA-MB-231 cells, namely motile fraction, persistence, invasion distance, and speed. These findings shed new light on the role of adipose tissue in cancer cell migration. They highlight the potential of our 3D printed breast cancer-stroma model to elucidate mechanisms of stroma-induced cancer cell migration and to serve as a screening platform for novel anti-cancer drugs targeting cancer cell dissemination.
Keyphrases
- cell migration
- adipose tissue
- insulin resistance
- papillary thyroid
- high fat diet
- breast cancer cells
- squamous cell
- childhood cancer
- extracellular matrix
- hyaluronic acid
- induced apoptosis
- poor prognosis
- high resolution
- skeletal muscle
- gene expression
- type diabetes
- stem cells
- risk assessment
- nlrp inflammasome
- single cell
- long non coding rna
- signaling pathway
- oxidative stress
- drug induced
- endoplasmic reticulum stress
- high glucose
- diabetic rats
- breast cancer risk
- wound healing