Roles of Metastasis Associated Fibroblasts in Paclitaxel Resistance of Brain Metastatic Tumor Cells: Evaluation in Metastatic Organoids.

BACKGROUNDSome breast cancer patients experience the devastating effects of brain metastases. The metastasis-associated fibroblasts (MAFs), the most abundant cells in the metastatic microenvironment, have an important role in chemoresistance. The MAFs' roles in paclitaxel resistance of brain metastatic tumor cells were evaluated in metastatic organoids.

METHODSBrain metastatic cells, known as 4T1B, were isolated and expanded from the brains of cancerous mice. Alginate-based metastatic organoids were prepared from the culture of 4T1B and 3T3 fibroblasts in an alginate solution. Cytotoxic activity of paclitaxel against 4T1B in 3D (3-Dimensional) culture was evaluated by MTT. For molecular analysis, real-time PCR was done.

RESULTSOur results proved that in brain metastatic organoids, fibroblasts cause a significant increase in paclitaxel resistance. Molecular analysis showed that the expression level of α-smooth muscle actin (α-SMA) increased in MAF compared to normal fibroblasts. Surprisingly, the expression level of fibroblast-specific protein 1 (FSP-1) decreased compared to normal fibroblasts.

CONCLUSIONHere, we reveal the pivotal roles of MAFs in chemoresistance and discuss their molecular properties. Our approach involves exploring various therapeutic techniques to comprehend MAFs and presenting therapeutic perspectives for metastatic cancer treatment.