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Human Brain Metastatic Stroma Attracts Breast Cancer Cells via Chemokines CXCL16 and CXCL12

Human Brain Metastatic Stroma Attracts Breast Cancer Cells via Chemokines CXCL16 and CXCL12

Brile Chung, Ali A Esmaeili, Sailesh Gopalakrishna-Pillai, John P Murad, Emily S Andersen, Naveen Kumar Reddy, Gayathri Srinivasan, Brian Armstrong, Caleb Chu, Young Kim, Tommy Tong, James Waisman, John H Yim, etc.

NPJ Breast Cancer. 2017 Mar 2;3:6.

PMID: 28649646

Abstract:

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. To further understand the interplay between cancer cells and cancer-associated fibroblasts from each site, we developed three-dimensional organoids composed of patient-derived primary or brain metastasis cancer cells with matching cancer-associated fibroblasts. Three-dimensional CAF aggregates generated from brain metastasis promote migration of cancer cells more effectively than cancer-associated fibroblast aggregates derived from primary tumor or normal breast stromal cells. Treatment with a CXCR4 antagonist and/or CXCL16 neutralizing antibody, alone or in combination, significantly inhibited migration of cancer cells to brain metastatic cancer-associated fibroblast aggregates. These results demonstrate that human brain metastasis cancer-associated fibroblasts potently attract breast cancer cells via chemokines CXCL12 and CXCL16, and blocking CXCR6-CXCL16/CXCR4-CXCL12 receptor-ligand interactions may be an effective therapy for preventing breast cancer brain metastasis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248567	CXCL16 human			Price

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