Identification of Pro‐Metastatic Signatures in Vesicles Released from Breast Cancer Primary Tumors

Abstract

Breast cancer is one of the deadliest cancers in the world. Effective metastasis of the primary tumor to the bone, brain, lungs, and other organs are the causes for morbidity of breast cancer patients. Therefore, there is a necessity to detect metastasis early for successful therapy. One approach for detecting metastases early is to identify ways in which metastatic breast cancers modify the blood by releasing particles from the cancer cells. Here we are testing the idea that metastatic breast cancer cells export particles that are different from nonmetastatic cells. To do so, we raised antibodies against particles exported from breast cancer cells. We then tested whether these antibodies could distinguish between low and high metastatic breast cancer cell lines, and breast cancer cells that have a propensity to metastasize to different organs. We found that antibodies detected CD81 and integrin alpha‐3 beta‐1 at much higher abundance in particles exported from low metastatic cells than high metastatic cells. This result supports the idea that CD81 and alpha‐3 beta‐1 integrin may be metastatic suppressors. In addition, we identified several other antibodies that bind differently to particles exported from the brain, bone, and lung specific organotropic breast cancer cells. Our findings suggest that particles exported from breast cancer cells change during metastatic progression, and raise the possibility that antibodies detecting such differences might be of prognostic value. Future work will identify the antigens for these antibodies, and test whether they can indeed distinguish organotropic metastases of breast cancer in blood plasma.