Metastasis is facilitated by cancer-associated fibroblasts (CAF) in the tumor microenvironment through mechanisms yet to be elucidated. In this study, we used a size-based microfilter technology developed by our group to examine whether circulating CAF identified by FAP and α-SMA co-expression (cCAF) could be distinguished in the peripheral blood of patients with metastatic breast cancer. In a pilot study of patients with breast cancer, we detected the presence of cCAFs in 30/34 (88%) patients with metastatic disease (MET group) and in 3/13 (23%) patients with localized breast cancer (LOC group) with long-term disease-free survival. No cCAFs as defined were detected in healthy donors. Further, both cCAF and circulating tumor cells (CTC) were significantly greater in the MET group compared with the LOC group. Thus, the presence of cCAF was associated with clinical metastasis, suggesting that cCAF may complement CTC as a clinically relevant biomarker in metastatic breast cancer.
Bibliographical noteFunding Information:
The authors thank the members of Drs. El-Ashry, Datar, and Lippman and Cote lab groups for thoughtful discussion. The authors also thank all the patients and healthy donors who kindly donated blood for this study. The authors thank Sakhi Phillips and Dr. Allan Pollack for their help in acquisition of prostate cancer samples. The authors thank the University of Miami Tissue Bank for their help in acquisition of colorectal cancer samples. Z. Ao and S.H. Shah thank partial support and assistance from the Sheila and David FuenteGraduate Program in Cancer Biology, Sylvester Comprehensive Cancer Center. This work was supported in part by DOD W81XWH-09-1-0050, NIH R21 5R21CA182050-02, R33 1R21CA123027-01/03 (R.J. Cote), and Sylvester Comprehensive Cancer Center Developmental Funds (D. El-Ashry).