Studying Breast Cancer Lung Metastasis Using a Multi-Compartment Microfluidic Device With a Mimetic Tumor-Stroma Interaction Model Publisher



Zarin B^{1, 2} ; Rafiee L¹ ; Abdollahi S^{2, 3} ; Vatani M^{2, 3} ; Hassani M^{2, 4} ; Sanatinezhad A^{2, 3, 4} ; Javanmard SH⁵ Show Affiliations
Source: Translational Oncology Published:2025

Abstract

Background: Understanding the mechanisms underlying the metastasis of breast cancer cells to the lungs is challenging, and appropriate simulation of the tumor microenvironment with mimetic cancer-stroma crosstalk is essential. β4 integrin is known to contribute to triggering a variety of different signaling cues involved in the malignant phenotype of cancer but its role in organ-specific metastasis needs further study. In this work, a multi-compartment microfluidic tumor model was developed to evaluate cancer cell invasion. Materials and methods: To model the primary tumor microenvironment, breast cancer cells (MCF7) and cancer-associated fibroblasts (CAFs) were co-cultured within the tumor compartment of the microfluidic chip while normal lung fibroblasts (NLFs) were seeded in a different compartment, as the secondary tumor site, separated from the tumor compartment via a Matrigel™ layer resembling the extracellular matrix. Results: The cytotoxic effect of β4 integrin blockade on cancer cells gradually increased after 48 and 72 h of co-culture. Invasion of breast cancer cells in both single and coculture models was characterized in response to β4 integrin blockade. The invasion rate and gap closure of MCF7/CAF_NLF was significantly higher than MCF7_NLF (P < 0.0001). β4 integrin inhibition reduced the rate of gap closure and invasion of both (P < 0.0001). Conclusions: Biomimetic microfluidic-based tumor models hold promise for studying cancer metastasis mechanisms. Precise manipulation, simulation, and analysis of the cancer microenvironment are made possible by microfluidics. © 2025