ADSC-Derived CCL8 Regulates HIF-1α Signaling and Promotes Colorectal Cancer Progression in a 3D Coculture Platform

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• The tumor microenvironment (TME) significantly influences cancer progression.
• Adipose tissue and its stem cells (ADSCs) are increasingly recognized as key components of the TME, particularly in colorectal cancer (CRC).
• Understanding the crosstalk between ADSCs and CRC cells is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the interactions between ADSCs and CRC cells within the TME.
• To elucidate the role of ADSCs in regulating CRC progression via cytokine signaling.
• To explore the underlying molecular mechanisms, including HIF-1-related pathways.

Main Methods:

• Human ADSCs were co-cultured with CRC cells using a 3D PDMS chip.
• Techniques included cytokine profiling, immunofluorescence, FACS, western blotting, qPCR, and immunoprecipitation.
• Analysis focused on interrogating HIF-1-related mechanisms and signaling pathways.

Main Results:

• ADSCs secrete CCL8, which significantly enhances CRC cell migration.
• ADSC-derived CCL8 activates the ERK pathway, increasing HIF-1α protein accumulation and p300 interaction in CRC cells.
• This leads to upregulated epithelial-mesenchymal transition markers and a more aggressive cancer phenotype.

Conclusions:

• ADSC-derived CCL8 is a key mediator of adipose-tumor crosstalk in CRC, driving progression through HIF-1α signaling.
• The study highlights the importance of the TME in amplifying oncogenic signaling.
• A 3D co-culture platform was validated as a relevant model for studying TME interactions in CRC.