The researchers were interested to see if the exosomes budding off of melanoma actually participated in the course of the cancer -- and they found that they do, and to a great extent.
"Upon their release from the primary tumor, exosomes derived from melanoma cells fuse with cells in distant metastatic organs and lymph nodes, mediating vascular leakiness and inflammation, thereby promoting the formation of pre-metastatic niches that enhance future metastatic growth," Dr. Lyden says.
According to Dr. Peinado, a number of exosomal proteins are transferred by the exosomes to BMDCs where they can reprogram or "educate" the cells to participate in the metastatic cascade. "We found an oncogenic protein, called MET, that is produced by highly metastatic tumors and packaged into pro-metastatic exosomes. The tumor exosomes circulate, fuse and transfer their information, including the MET oncoprotein, to many cells, such as bone marrow cells, which in turn promote a pro-metastatic phenotype," he says.
They also discovered that the education of BMDCs by exosomes is long-lasting, and this may explain how a tumor dormant for decades suddenly develops metastatic disease. These findings are crucial, says Dr. Bromberg, because "educated bone marrow is the key in disease recurrence and may even foster a future secondary cancer."
Examining human blood samples, the scientists found a distinct signature of exosomal proteins (including MET) in patients with stage IV, widely metastatic melanoma that was not found in blood exosomes from patients with non-metastatic melanoma.
They say this protein signature could be used to predict which patients with stage III disease and local lymph node metastasis would then go on to develop distant metastatic disease. "Treatment modalities could be initiated earlier in these high-risk patients to prevent disease progression," Dr. Lyden says. "Our results demonstrated that MET oncoprotein
|Contact: Lauren Woods|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College